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Blood, Vol. 90 No. 7 (October 1), 1997:
pp. 2535-2540
RAPID COMMUNICATION
Fusion of TEL, the ETS-Variant Gene 6 (ETV6), to the Receptor-Associated Kinase JAK2 as a Result of t(9; 12) in a Lymphoid and t(9; 15; 12) in a Myeloid Leukemia
By
Pieter Peeters,
Sophie D. Raynaud,
Jan Cools,
Iwona Wlodarska,
Josiane Grosgeorge,
Patrick Philip,
Fabrice Monpoux,
Luc Van Rompaey,
Mathijs Baens,
Herman Van den Berghe, and
Peter Marynen
From the Center for Human Genetics, Flanders Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium; Laboratoire de Génétique, Faculté de Médecine, Nice; UEFCT, Hôpital Pasteur, Nice; and Service de Pédiatrie, Hôpital de l'Archet, Nice, France.
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ABSTRACT |
Translocations in hematologic disease of myeloid or lymphoid origin with breakpoints at chromosome band 12p13 frequently result in rearrangements of the Ets variant gene 6 (ETV6). As a consequence either the ETS DNA-binding domain or the Helix-Loop-Helix (HLH) oligomerization domain of ETV6 is fused to different partner genes. We show here that a t(9; 12)(p24; p13) in a case of early pre-B acute lymphoid leukemia and a t(9; 15; 12)(p24; q15; p13) in atypical chronic myelogenous leukemia in transformation involve the ETV6 gene at 12p13 and the JAK2 gene at 9p24. In each case different fusion mRNAs were found, with only one resulting in an open reading frame for a chimeric protein consisting of the HLH oligomerization domain of ETV6 and the protein tyrosine kinase (PTK) domain of JAK2. The cloning of the complete human JAK2 coding and genomic sequences and of the genomic junction fragments of the translocations allowed a characterization of the different splice events leading to the various mRNAs. JAK2 plays a central role in non-protein tyrosine kinase receptor signaling pathways, which could explain its involvement in malignancies of different hematologic lineages. Besides hop in Drosophila no member of the JAK family has yet been implicated in tumorigenesis.
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INTRODUCTION |
RECURRING ABNORMALITIES of the short arm of chromosome 9 and 12 have been identified as being among the more common cytogenetic rearrangements in acute lymphoblastic leukemia (ALLs) in children, with reported incidence of between 7% and 15%.1-5 Both regions are frequently involved in structural variations including deletions and unbalanced translocations resulting in the loss of 9p and 12p material, and apparently balanced reciprocal translocations, all involving the regions 9p11-p24 and 12p12-p13.
Cytogenetic alterations of the 12p12-p13 chromosomal bands are detected in about 10% of childhood ALLs.5,6 The translocations involve several partner chromosomes and can be associated with interstitial or terminal deletions that account for up to 50% of the cytogenetically detectable 12p abnormalities.4-7 In fact, recently published results indicate that alterations of the 12p12-p13 region are largely underestimated by standard cytogenetics. ETV6 (also known as TEL) was cloned at the breakpoint of the t(5; 12)(q33; p13) present in myelomonocytic leukemic cells.8 More recently, ETV6 has been shown to be fused to a number of different partners as a result of various leukemia associated translocations.9-15 In ALL, ETV6 was found to be fused to ABL in some rare cases with t(9; 12)(q34; p13),11 and ETV6/AML1 fusion transcripts, resulting from cryptic t(12; 21),12,13 were detected in 22% to 27% of the cases with childhood B-lineage ALL, representing the most common known gene rearrangement in cancer of childhood.16-18 We and others have previously shown that t(12; 21) and deletion of the nontranslocated ETV6 allele are frequently associated.16,17,19
We here report the identification of JAK2 as a fusion partner of ETV6 in t(9; 12)(p24; p13) found in leukemic cells of a child with early B-precursor ALL and in t(9; 15; 12) (p24; q15; p13) found in an adult patient with atypical CML. In both cases this translocation results in the fusion of the HLH domain of ETV6 to the protein tyrosine kinase domain of the receptor associated kinase JAK2.
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MATERIALS AND METHODS |
Patient material.
The first patient, a 19-month-old boy, was admitted to the hospital with hyperthermia, palor, petechiae, splenomegaly, and detectable lymph nodes. Laboratory findings at diagnosis showed 4.4 mmol/L hemoglobine, platelet count 1 × 1010/L, leukocyte count 550 × 109/L, and the presence of 100% blast cells in peripheral blood. The bone marrow (BM) was infiltrated by small blasts of homogeneous size with high nuclear-cytoplasmic ratio, thus establishing a diagnosis of ALL L1 according to the French-American-British (FAB) classification. Immunophenotypic analysis of the blasts showed an early pre-B lineage ALL (CD10+, CD19+, CD20+, CD34+, slg-, Cµ-, HLA-DR+). There were no signs of central nervous system involvement. The patient was enrolled for an intensive chemotherapy regimen according to the European Organisation for Radiotherapy and Chemotherapy (EORTC) protocol 58881. At the end of induction therapy the patient achieved complete hematological remission (CR), which was maintained for 14 months, continuing the treatment according to the protocol. After 7 months of consolidation courses, the patient suffered BM plus overt testicular relapse, with approximately 4% blastic invasion of the BM. Salvage therapy was started and CR was obtained. This second course of this high-dose chemotherapy was interrupted as the patient suddenly became lethargic, hypotonic and mutic, and rapidly developed clinical features of secondary Parkinsonism. A basal ganglia necrosis of toxic origin was diagnosed. Cerebrospinal fluid remained normal. The parents refused further antileukemic therapy. After few months of therapeutic abstention, maintenance therapy was started again. The boy is now in continuous CR of ALL, 31 months after diagnosis. The second patients clinical history was already described.14 Briefly, clinical examination showed a slight splenomegaly. Hematologic data were as follows: hemoglobin level 8.7 g/dL; platelet count 37 × 109; white blood cell count 64 × 109/L with 27% neutrophils, 11% lymphocytes, and 11% lymphoblasts. BM was hypercellular with a proportion of 25% of blast cells with a myeloid morphology, 19% of promyelocytes, 14% of myelocytes, and 14% of eosinophils. The diagnosis of atypical chronic myelogenous leukemia (CML) in transformation was established.
Cytogenetic studies.
The initial analysis, at diagnosis, was made on BM cells. Cells were cultured for 16 and 24 hours in vitro without stimulation. Chromosomes were identified using RHG (R-bands by heating using Giemsa) banding techniques and classified according to International System for Cytogenetic Nomenclature (ISCN) (1995).20 The karyotype in the ALL case was abnormal in twelve metaphases, 45,XY, t(9; 12)(p23; p13), t(13; 21). One additional metaphase presented the t(13; 21) as sole rearrangement. The constitutional origin of the t(13; 21) was already known as the mother had undergone a prenatal diagnosis for late in life pregnancy. The same abnormal karyotype was observed at the time of relapse in cells of testicular and medullary biopsies, without additional secondary abnormalities. Cytogenetic analysis performed in the CML case at the time of diagnosis showed clonal chromosomal abnormalities in 100% (6 of 6) of analyzed BM cells described as 46,XY, t(3; 12)(q26; p13), t(9; 15; 12)(p24; q15; p13).
Fluorescence in situ hybridization (FISH) analysis.
FISH was performed as previously described.21,22 Biotin-labeled probes were prepared by nick translation (Bio Nick Kit; GIBCO-BRL, Gaithersburg, MD). Whole chromosome painting probes for chromosomes 9 and 12 (Coatasome; Oncor, Gaithersburg, MD) or a chromosome 12 centromere probe were used if necessary to assert the location of the FISH signals. The presence of FISH signals was scored on an average of 23 abnormal metaphases (15 to 52) per probe.
Polymerase chain reaction (PCR) and cloning.
Total RNA was isolated from BM using the Trizol reagent (GIBCO-BRL). First-strand cDNA was reverse transcribed from 1 µg of total RNA with MuMLV-reverse transcriptase (GIBCO-BRL) according to standard procedures using the primer R2N6 (5'-CCAGTGAGCAGAGTGACGAGGACTCGAGCTCAAGC(N)6-3' ). Nested PCR was performed using primers specific for exon 4 of ETV6 (ALL case), namely ETV6F1 (5'-TTCCACCCTGGAAACTCTATA-3' ) and ETV6F2 (5'-ATACACACACAGCCGGAGGTC-3' ) or exon 5 (CML case), ETV6F3 (5'-ATGCACCCTCTGATCCTGAACC-3' ) and ETV6F4 (5'-GAAGACCTGGCTTACATGAAC-3' ) in combination with primers R2N R16 (5'-CCAGTGAGCAGAGTGACG-3' ) and R2N6R2 (5'-GAGGACTCGAGCTCAAGC-3' ). PCR products were cloned following standard procedures.
The ETV6-JAK2 fusion was confirmed by reverse transcriptase (RT)-PCR on patient RNA using the Titan RT-PCR system (Boehringer Mannheim, Mannheim, Germany), with the following primers: ETV6F1 in combination with JAK2R1 (5'-AAGGTTTGCTAATTCTGCCCACTTTGGTGC-3' ) specific for exon 17 of JAK2 (ALL case) and primer ETV6F3 in combination with JAK2R2 (5'-TGGTGAGGTTGGTACATCAG-3' ) specific for exon 12 of JAK2 (CML case).
Long-range PCR was performed using the Expand long template PCR system (Boehringer) with primers ETV6F1 and ETV6F2 in combination with JAK2R1 (ALL case) and primers ETV6F3 and ETV6F4 in combination with JAK2R2 (CML case).
The human JAK2 cDNA was isolated by screening a  DR2 human BM cDNA library (Clontech, Palo Alto, CA) and by 3'RACE on fetal brain cDNA (Clontech). Several overlapping clones were sequenced to obtain the complete sequence from both strands (Genbank accession no. AF005216).
DNA sequencing and analysis.
Nucleotide sequence was determined by dideoxynucleotide chain termination with fluorescein isothiocyanate (FITC)-labeled primers and analyzed on ALF sequencer (Pharmacia, Uppsala, Sweden). Database searching was carried out by using the BLASTN algorithm on the NIH Blast server.23
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RESULTS |
Cytogenetic analysis at diagnosis of a patient with pre-B ALL showed the presence of a t(9; 12)(p24; p13) as the only chromosomal anomaly associated with the disease. FISH using cosmids derived from a contig spanning the ETV6 gene24 located at 12p13 showed the involvement of this gene: a signal on the normal chromosome 12 and the der(9) was observed with cosmid 163E7, containing exons 3 to 5 of ETV6 whereas cosmid 54D5, containing exons 5 to 8, showed a signal on normal and der(12) (Fig 1), suggesting the 12p breakpoint to be located between exon 4 and 5 of ETV6. The second case, a patient diagnosed with CML in blast crisis, was previously studied because of the presence of a t(3; 12) that resulted in a fusion between ETV6 and MDS1-EVI1 on 3q26.14 At that time it was shown that the other ETV6 allele was involved in a complex t(9; 15; 12) (p24; q15; p13). FISH analysis with cosmid 54D5 showed a `split' signal with the probe hybridizing to the der(12) t(3; 12), the der(12)t(9; 15; 12), and the der(9)t(9; 15; 12), suggesting a breakpoint between exon 5 and 6 of ETV6 (Fig 1).
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| Fig 1.
FISH analysis of the ETV6 and JAK2 rearrangements in the ALL case (A and B) and the ALL case (C and D). Hybridization with cosmid 54D5, which spans the 12p13 breakpoint in the CML case, is shown in (A) and (C). Thick arrows indicate the der(12), thin arrows indicate the der(9), and the arrowhead points to the normal 12. (B and D) Hybridization with a mixture of the PACs containing JAK2 and spanning the 9p24 breakpoint. Thin and thick arrows indicate, respectively, the der(9) and the der(12); the arrowhead shows the der(15)t(9; 15; 12); 9N indicates the normal chromosome 9. In (C) and (D) hybridization of a centromere 12 probe is shown in white.
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To identify the eventual fusion partner of ETV6, RNA from the patients was reverse transcribed using a random hexanucleotide primer described above. 3'-RACE was performed using nested primers located in exon 4 and 5 of ETV6, respectively. Sequence analysis of the amplification products detected in both cases novel sequences fused to the ETV6 sequence conserving the open reading frame. This novel sequence showed homology to the murine JAK2 kinase25 (90% identity), strongly suggesting that they were derived from the human JAK2.
With these probes, a human JAK2 cDNA was isolated from a human BM cDNA library and completed by 3'-RACE experiments on fetal brain cDNA. In total 4,161 bp of JAK2 cDNA sequence was isolated, including an open reading frame encoding a protein of 1,132 amino acids. This protein is 92% identical (at the amino acid level) to murine JAK2 and 94% identical to the rat JAK2, consistent with its identity as the human JAK2. Using the same probes three P1 artificial chromosome (PAC) clones were isolated from a human genomic PAC library. Analysis of these clones showed that the JAK2 gene consists of 24 exons spanning at least 140 kb (manuscript in preparation). FISH with these genomic clones confirmed the mapping of JAK2 to 9p24 as was previously suggested using a murine probe26 and showed the clones to cross the breakpoint in both leukemias (Fig 1).
Taken together the data indicated a fusion of exon 4 of ETV6 to exon 17 of JAK2 in the ALL case and a fusion of exon 5 of ETV6 to exon 12 of JAK2 in the CML case. When primers were derived for the respective exons to confirm this directly by RT-PCR, two fragments were unexpectedly detected in the ALL case (Fig 2). Sequence analysis showed the smaller, more abundant, product to result from the splicing of exon 4 of ETV6 to exon 17 of JAK2, while the larger product spliced exon 4 of ETV6 to exon 16 of JAK2. Only the first results in an open reading frame linking the HLH oligomerization domain of ETV6 to part of the JH2 and the complete protein tyrosine kinase domain of JAK2. To confirm this observation at the genomic level, long-range PCR was performed on tumor DNA using primers located in the relevant exons of ETV6 and JAK2. Sequencing then showed that the breakpoint in JAK2 indeed occurred at the genomic level between exons 15 and 16 (Fig 3, top). RT-PCR experiments failed to detect a reciprocal transcript, suggesting that the ETV6/JAK2 fusion has oncogenic properties in this case.
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| Fig 2.
RT-PCR analysis of ETV6/JAK2 fusion products. Total RNA from the ALL case (lane 1), the CML case (lane 2), and normal WBCs (lane 3) was used in a RT-PCR with primers located in the relevant exons of ETV6 and JAK2 (see Materials and Methods section). In each case a major product is observed, together with a minor product of a larger size. The different PCR products are the result of alternative splicing events as shown in Fig 3. Marker size is indicated to the left.
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| Fig 3.
Genomic structure of the different translocations and resulting open reading frames. The upper panel shows the results for the ALL case, the lower panel for the CML case. On top of each panel the genomic structure of the junction fragment is shown. The ETV6 gene is represented by a thin line, the JAK2 gene by a thick line, and a fragment of unknown origin by an open bar. The boxes show the different exons. The sequence of the breakpoints is shown on top of the genomic structure. In the ALL case ETV6 genomic sequences are shown in capitals, JAK2 sequences in lowercase. Two splice variants are observed, the first fusing exon 4 of ETV6 to exon 16 of JAK2. The second splices exon 4 to exon 17 of JAK2. In the CML case exon 5 of ETV6 is spliced either to an exon (U) in the sequence of unknown origin which is then spliced to a cryptic acceptor site within exon 11 of JAK2 or directly to exon 12 of JAK2. ETV6 and JAK2 genomic sequences are indicated in uppercase letters, and a genomic sequence of unknown origin in lowercase letters. Splice donor and acceptor sites for the exon within this sequence are in boldface type. The composition of the fusion proteins encoded by the different splice variants is shown with the sequence of the junction fragments underneath. Arrows indicate the breakpoints. E, EcoRI site; HLH, oligomerization domain of ETV6; JH2, pseudokinase domain of JAK2; PTK, protein tyrosine kinase domain of JAK2.
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A similar RT-PCR analysis of the CML case interestingly also yielded two products, the smaller being more abundant as judged by RT-PCR (Fig 2). The larger amplification product fused exon 5 of ETV6 to a cryptic exon located in the intervening genomic sequence (see below) and a cryptic acceptor site within exon 11 of JAK2. The smaller one fused exon 5 of ETV6 to exon 12 of JAK2, only this resulted in an open reading frame linking the ETV6 HLH oligomerization domain to the JH2 and protein kinase domain of JAK2. Cloning of the genomic breakpoint by long-range PCR indeed detected a 3,600-bp sequence of unknown origin between the ETV6 and JAK2 sequences. This sequence contained the cryptic exon found in the larger RT-PCR product (Fig 3). No reciprocal transcript could be detected by RT-PCR as expected for a three-way translocation. The significance of the complex splice events observed in both cases is not known, but the observation could be relevant for those cases where a fusion of ETV6 apparently does not lead to a fusion protein.
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DISCUSSION |
The involvement of JAK2 in large number of noncatalytic receptor signaling pathways has been shown extensively over the past few years.27-29 In Drosophila, a dominant gain-of-function mutation of a JAK homologue encoded by the hopsctoch (hop) gene, was reported to result in neoplastic growth. Here a single amino acid change in hop causes a leukemia-like disease in the fly.30 Although constitutive activation of the JAK-STAT pathway was shown in HTLV-1-infected peripheral blood T cells31 and selective growth inhibition of acute lymphoblastic cells has been accomplished, both in vivo and in vitro, by using a specific JAK2 tyrosine kinase blocker,32 no oncogenic activity has been reported for mammalian JAKs.
Reports on an artificial CD16/CD7/Jak2 and an epidermal growth factor receptor/Jak2 fusion protein suggest that Jak2 may become activated by homodimerization.33,34 In these reports it was shown that cross-linking of Jak2 results in autophosphorylation, although the activated pathways seem to differ in both systems. Moreover, in the latter it was shown that activation of Jak2 seems to be sufficient for transducing a growth signal in hematopoietic cells. There is clear evidence that the ETV6 HLH domain provides a self-association motif to the ETV6-PDGFRB oncogenic fusion protein, which results from a t(5; 12) in myelodysplastic disease.35,36 Moreover, this motif was shown to be essential to the chimeric protein to activate the PDGFRB kinase-dependent signaling pathways.35 The same mitogenic properties depending on the HLH domain of ETV6 were shown for the ETV6-ABL oncoprotein associated with t(9; 12).37 In view of these findings a model for the mechanisms of transformation by the ETV6/JAK2 fusion could be proposed where the HLH domain of ETV6 provides a dimerization interface to the kinase domain of JAK2, thus activating JAK2. Interestingly, in the CML case both alleles of ETV6 are affected by translocation. Besides the ETV6/JAK2 fusion, an ETV6/MDS1/EVI1 is also present in the leukemic cells of this patient.14 It is clear that in addition to the effect of the putative fusion proteins that result from the chromosomal rearrangements, the fact that ETV6 can no longer exert its normal function could also contribute to the oncogenic process. However, it should be noted that in both cases a minor mRNA species is formed that potentially codes for an independent HLH domain of ETV6 (Fig 3). The eventual effect of this domain on the ETV6/JAK2 fusion protein remains to be evaluated.
The presence of two fusion genes involving ETV6 in the CML case also raises questions with regard to the involvement of each fusion in the oncogenic process. The involvement of EVI1 in blast crisis in CML has been reported.38 One might speculate that the blast crisis in the present case is related to the ETV6/MDS1/EVI1 fusion, whereas the ETV6/JAK2 fusion would be an earlier event. Unfortunately, no previous samples of the patient are available to test this hypothesis.
The putative involvement of ETV6/JAK2 fusions in both myeloid and lymphoid malignancies is unusual and could be explained by the involvement of the JAK2 kinase in multiple signaling pathways. It should be noted that in the ALL case only part of the JH2 domain is present in the fusion, whereas the complete JH2 domain is present in the fusion found in the myeloid case. Recently it was shown39 that JAK2 activates Raf-1 via p21ras, thus linking JAK2 to the PDGFRB kinase-dependent signaling pathways which appear activated by the t(5; 12) in myeloid malignancies.35 This raises the question of whether the JH2 domain of JAK2, whose specific role is not known, is involved in the determination of the specific pathways activated by the ETV6/JAK2 fusion protein.
In conclusion, we now have the appropriate tools to investigate JAK2 involvement through chromosomal rearrangements in human neoplasia by FISH analysis. Furthermore, we show that dissection of complex chromosomal rearrangements can lead to the identification of different putative actors in leukemiogenesis for each of the observed abnormalities. Also, the occurrence of variant splicing has to be considered during the analysis of other translocations involving ETV6 or JAK2. Finally, to elucidate the potential role of the JH2 domain of JAK2 in the lineage specificity of the putative fusion proteins, a dissection of the pathways activated by the different ETV6/JAK2 fusions will be needed.
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FOOTNOTES |
Submitted July 8, 1997;
accepted July 22, 1997.
Supported by the CNRS, a grant from the Ligue nationale Française Contre le Cancer, a grant from the Association pour la Recherche sur le Cancer, and Grant No. G 0153.96 of the FWO-Vlaanderen. P.M. is an `onderzoeksdirecteur' and M.B. a "postdoctoraal onderzoeker" of the FWO-Vlaanderen; P.P. is the recipient of a scholarship of the IWT.
Address reprint requests to Peter Marynen, PhD, Center for Human Genetics, University of Leuven, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.
The publication costs of this article were defrayed in part by page
charge payment. This article must therefore be hearly marked
``advertisment'' in accordance with 18 U.S.C. section 1734 solely to
indicate this fact.
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ACKNOWLEDGMENT |
We thank A. Criel and D. Selleslagh for patient material, B. Brunet for technical support of cytogenetics, and R. Gratery for artwork.
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REFERENCES |
1.
Kowalczyk J,
Sandberg AA:
A possible subgroup of ALL with 9p-.
Cancer Genet Cytogenet
9:383,
1983[Medline]
[Order article via Infotrieve]
2.
Chilcote RR,
Brown E,
Rowley JD:
Lymphoblastic leukemia with features associated with abnormalities of the short arm of chromosome 9.
N Engl J Med
313:286,
1985[Abstract]
3.
Pollack C,
Hagemeijer A:
Abnormalities of the short arm of chromosome 9 with partial loss of material in hematological disorders.
Leukemia
1:541,
1987[Medline]
[Order article via Infotrieve]
4.
Groupe Français de Cytogénétique Hématologique (GFCH):
Collaborative study of karyotypes in childhood acute lymphoblastic leukemias.
Leukemia
7:10,
1993[Medline]
[Order article via Infotrieve]
5.
Raimondi SC:
Current status of cytogenetic research in childhood acute lymphoblastic leukemia.
Blood
81:2237,
1993[Free Full Text]
6.
Raimondi SC,
Williams DL,
Callihan T,
Peiper S,
Rivera GK,
Murphy SB:
Nonrandom involvement of the 12p12 breakpoint in chromosome abnormalities of childhood acute lymphoblastic leukemia.
Blood
68:69,
1986[Abstract/Free Full Text]
7. Mitelman F (ed): Catalog of Chromosome Aberrations in Cancer (ed 5). New York, NY, Liss, 1994
8.
Golub TR,
Barker GF,
Lovett M,
Gilliland DG:
Fusion of PDGF receptor  to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5; 12) chromosomal translocation.
Cell
77:307,
1994[Medline]
[Order article via Infotrieve]
9.
Buijs A,
Sherr S,
van Baal S,
van Bezouw S,
van der Plas D,
Geurts van Kessel A,
Riegman P,
Lekanne Deprez R,
Zwarthoff E,
Hagemeijer A,
Grosveld G:
Translocation t(12; 22)(p13; q11) in myeloproliferative disorders results in fusion of the ETS-like TEL gene on 12p13 to the MN1 gene on 22q11.
Oncogene
10:1511,
1995[Medline]
[Order article via Infotrieve]
10.
Wlodarska I,
Mecucci C,
Marynen P,
Guo C,
Franckx D La Starza R,
Aventin A,
Bosly A,
Martelli MF,
Cassiman JJ,
Van den Berghe H:
TEL gene is involved in myelodysplastic syndromes with either the typical t(5; 12)(q33; p13) translocation or its variant t(10; 12)(q24; p13).
Blood
85:2848,
1995[Abstract/Free Full Text]
11.
Papadopoulos P,
Ridge SA,
Boucher CA,
Stocking C,
Wiedemann LM:
The novel activation of ABL by fusion to an ets-related gene, TEL.
Cancer Res
55:34,
1995[Abstract/Free Full Text]
12.
Romana SP,
Mauchauffé M,
Le Coniat M,
Chumakov I,
Le Paslier D,
Berger R,
Bernard OA:
The t(12; 21) of acute lymphoblastic leukemia results in a TEL-AML1 gene fusion.
Blood
85:3662,
1995[Abstract/Free Full Text]
13.
Golub TR,
Barker GF,
Bohlander SK,
Hiebert SW,
Ward DC,
Brayward P,
Morgan E,
Raimondi SC,
Rowley JD,
Gilliland DG:
Fusion of the tel gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia.
Proc Natl Acad Sci USA
92:4917,
1995[Abstract/Free Full Text]
14.
Peeters P,
Wlodarska I,
Baens M,
Criel A,
Selleslag D,
Hagemeijer A,
Van Den Berghe H,
Marynen P:
Fusion of ETV6 to MDS1/EVI1 as a result of t(3; 12)(q26; p13) in myeloproliferative disorders.
Cancer Res
57:564,
1997[Abstract/Free Full Text]
15.
Suto Y,
Sato Y,
Smith SD,
Rowley JD,
Bohlander SK:
A t(6; 12)(q23; p13) results in the fusion of ETV6 to a novel gene, STL, in a B-cell ALL cell line.
Genes Chrom Cancer
18:254,
1997[Medline]
[Order article via Infotrieve]
16.
Romana S,
Poirel H,
Leconiat M,
Flexor MA,
Mauchauffe M,
Jonveaux P,
Macintyre EA,
Berger R,
Bernard OA:
High frequency of t(12; 21) in childhood B-lineage acute lymphoblastic leukemia.
Blood
86:4623,
1995
17.
Shurtleff SA,
Buijs A,
Behm FG,
Rubnitz JE,
Raimondi SC,
Hancock ML,
Chan GC,
Pui CH,
Grosveld G,
Downing JR:
TEL/AML1 fusion resulting from a cryptic t(12; 21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis.
Leukemia
9:1985,
1995[Medline]
[Order article via Infotrieve]
18.
Cayuela JM,
Bruchel A,
Orange C,
Madani A,
Auclerc MF,
Daniel MT,
Schaison G,
Sigaux F:
TEL-AML1 fusion RNA as a new target to detect minimal residual disease in pediatric B-cell precursor acute lymphoblastic leukemia.
Blood
88:302,
1996[Abstract/Free Full Text]
19.
Raynaud S,
Cavé H,
Baens M,
Bastard C,
Cacheux V,
Grosgeorge J,
Guidal-Giroux C,
Guo C,
Vilmer E,
Marynen P,
Grandchamp B:
The 12; 21 translocation involving TEL and deletion of the other TEL allele: Two frequently associated alterations found in acute lymphoblastic leukemia.
Blood
87:2891,
1996[Abstract/Free Full Text]
20. Mitelman F (ed): An International System for Human Cytogenetic Nomenclature. Basel, Switzerland, Karger, 1995
21.
Raynaud SD,
Baens M,
Grosgeorge J,
Rodgers K,
Reid CDL,
Dainton M,
Fuzibet JG,
Gratecos N,
Taillan B,
Ayraud N,
Marynen P:
Fluorescence in situ hybridization analysis of t(3; 12)(q26; p13): A recurring chromosomal abnormality involving the TEL gene (ETV6) in myelodysplastic syndromes.
Blood
88:682,
1996[Abstract/Free Full Text]
22.
Dierlamm J,
Wlodarska I,
Michaux L,
La Starza R,
Zeller W,
Mecucci C,
Van Den Berghe H:
Successful use of the same slide for consecutive fluorescence in situ hybridization experiments.
Genes Chrom Cancer
16:261,
1996[Medline]
[Order article via Infotrieve]
23.
Altschul SF,
Miller WW,
Myers EW,
Lipman DJ:
Basic local alignment search tool.
J Mol Biol
215:403,
1990[Medline]
[Order article via Infotrieve]
24.
Baens M,
Peeters P,
Guo C,
Aerssens J,
Marynen P:
Genomic organization of TEL: The human ETS-variant gene 6.
Genome Res
6:404,
1996[Abstract/Free Full Text]
25.
Silvennoinen O,
Witthuhn BA,
Quelle FW,
Cleveland JL,
Yi T,
Ihle JN:
Structure of the murine Jak2 protein-tyrosine kinase and its role in interleukin 3 signal transduction.
Proc Natl Acad Sci USA
90:8429,
1993[Abstract/Free Full Text]
26.
Pritchard MA,
Baker E,
Callen DF,
Sutherland GR,
Wilks AF:
Two members of the JAK family of protein kinases map to chromosomes 1p31.3 and 9p24.
Mamm Genome
3:36,
1992[Medline]
[Order article via Infotrieve]
27.
Wilks AF,
Oates AC:
The JAK/STAT pathway.
Cancer Surv
27:139,
1996[Medline]
[Order article via Infotrieve]
28.
Ihle JN:
Cytokine receptor signalling.
Nature
377:591,
1995[Medline]
[Order article via Infotrieve]
29.
Schindler C,
Darnell JE Jr:
Transcriptional responses to polypeptide ligands: The JAK/STAT pathway.
Annu Rev Biochem
64:621,
1995[Medline]
[Order article via Infotrieve]
30.
Harrison AD,
Binari R,
Nahreini TS,
Gilman M,
Perrimon N:
Activation of a Drosophila Janus kinase (JAK) causes hematopoietic neoplasia and developmental defects.
EMBO J
14:2857,
1995[Medline]
[Order article via Infotrieve]
31.
Xu X,
Kang SH,
Heidenreich O,
Okerholm M,
O'Shea JJ,
Nerenberg MI:
Constitutive activation of different Jak tyrosine kinases in human T cell leukemia virus type 1 (HTLV-1) tax protein or virus-transformed cells.
J Clin Invest
96:1548,
1995
32.
Meydan N,
Grunberger T,
Dadi H,
Shahar M,
Arpaia E,
Lapidot Z,
Leeder JS,
Freedman M,
Cohen A,
Gazit A,
Levitzki A,
Roifman CM:
Inhibition of acute lymphoblastic leukemia by a Jak-2 inhibitor.
Nature
379:645,
1996[Medline]
[Order article via Infotrieve]
33.
Sakai I,
Nabell L,
Kraft AS:
Signal transduction by a CD16/CD7/Jak2 fusion protein.
J Biol Chem
270:18420,
1995[Abstract/Free Full Text]
34.
Nakamura N,
Chin H,
Miyasaka N,
Miura O:
An epidermal growth factor receptor/Jak2 tyrosine kinase domain chimera induces tyrosine phosphorylation of Stat5 and transduces a growth signal in hematopoietic cells.
J Biol Chem
271:19483,
1996[Abstract/Free Full Text]
35.
Carroll M,
Tomasson MH,
Barker GF,
Golub TR,
Gilliland DG:
The TEL platelet-derived growth factor receptor (PDGFR) fusion in chronic myelomonocytic leukemia is a transforming protein that self-associates and activates PDGFR kinase-dependent signaling pathways.
Proc Natl Acad Sci USA
93:14845,
1996[Abstract/Free Full Text]
36.
Jousset C,
Carron C,
Boureux A,
Quang CT,
Oury C,
Dusanter-Fourt I,
Charon M,
Levin J,
Bernard O,
Ghysdael J:
A domain of TEL conserved in a subset of ETS proteins defines a specific oligomerization interface essential to the mitogenic properties of the TEL-PDGFR oncoprotein.
EMBO J
16:69,
1997[Medline]
[Order article via Infotrieve]
37.
Golub TR,
Goga A,
Barker GF,
Afar DE,
McLaughlin J,
Bohlander SK,
Rowley JD,
Witte ON,
Gilliland DG:
Oligomerization of the ABL tyrosine kinase by the Ets protein TEL in human leukemia.
Mol Cell Biol
16:4107,
1996[Abstract]
38.
Mitani K,
Ogawa S,
Tanaka T,
Miyoshi H,
Kurokawa M,
Mano H,
Yazaki Y,
Ohki M,
Hirai H:
Generation of the AML1-EVI1 fusion gene in the t(3; 21)(q26; q22) causes blastic crisis in chronic myelocytic leukemia.
EMBO J
13:504,
1994[Medline]
[Order article via Infotrieve]
39.
Xia K,
Mukhopadhyay NK,
Inhorn RC,
Barber DL,
Rose PE,
Lee RS,
Narsimhan RP,
D'Andrea AD,
Griffin JD,
Roberts TM:
The cytokine-activated tyrosine kinase JAK2 activates Raf-1 in a p21ras-dependent manner.
Proc Natl Acad Sci USA
93:11681,
1996[Abstract/Free Full Text]
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
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3036 - 3045.
|
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|
|
|
|
M B K Lambros, D S P Tan, R L Jones, R Vatcheva, K Savage, N Tamber, K Fenwick, A Mackay, A Ashworth, and J S Reis-Filho
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[PDF]
|
|
|
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94(2):
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[Full Text]
[PDF]
|
|
|
|
|
|
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. F. Tam, T.-L. Gu, J. Chen, B. H. Lee, L. Bullinger, S. Frohling, A. Wang, S. Monti, T. R. Golub, and D. G. Gilliland
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September 1, 2008;
112(5):
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
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J. Sayyah, A. Magis, D. A. Ostrov, R. W. Allan, R. C. Braylan, and P. P. Sayeski
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7(8):
2308 - 2318.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Hintzen, C. Evers, B. E. Lippok, R. Volkmer, P. C. Heinrich, S. Radtke, and H. M. Hermanns
Box 2 Region of the Oncostatin M Receptor Determines Specificity for Recruitment of Janus Kinases and STAT5 Activation
J. Biol. Chem.,
July 11, 2008;
283(28):
19465 - 19477.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Wernig, J. R. Gonneville, B. J. Crowley, M. S. Rodrigues, M. M. Reddy, H. E. Hudon, C. Walz, A. Reiter, K. Podar, Y. Royer, et al.
The Jak2V617F oncogene associated with myeloproliferative diseases requires a functional FERM domain for transformation and for expression of the Myc and Pim proto-oncogenes
Blood,
April 1, 2008;
111(7):
3751 - 3759.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Monni, L. Haddaoui, A. Naba, I. Gallais, M. Arpin, P. Mayeux, and F. Moreau-Gachelin
Ezrin is a target for oncogenic Kit mutants in murine erythroleukemia
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March 15, 2008;
111(6):
3163 - 3172.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Ferrajoli, S. Faderl, Q. Van, P. Koch, D. Harris, Z. Liu, I. Hazan-Halevy, Y. Wang, H. M. Kantarjian, W. Priebe, et al.
WP1066 Disrupts Janus Kinase-2 and Induces Caspase-Dependent Apoptosis in Acute Myelogenous Leukemia Cells
Cancer Res.,
December 1, 2007;
67(23):
11291 - 11299.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Tefferi and A. Pardanani
Evaluation of 'Increased' Hemoglobin in the JAK2 Mutations Era: A Diagnostic Algorithm Based on Genetic Tests
Mayo Clin. Proc.,
May 1, 2007;
82(5):
599 - 604.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. R. dos Santos, D. S. Rickman, A. de Reynies, F. Cormier, M. Williame, C. Blanchard, M.-H. Stern, and J. Ghysdael
Pre-TCR expression cooperates with TEL-JAK2 to transform immature thymocytes and induce T-cell leukemia
Blood,
May 1, 2007;
109(9):
3972 - 3981.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Malinge, R. Ben-Abdelali, C. Settegrana, I. Radford-Weiss, M. Debre, K. Beldjord, E. A. Macintyre, J.-L. Villeval, W. Vainchenker, R. Berger, et al.
Novel activating JAK2 mutation in a patient with Down syndrome and B-cell precursor acute lymphoblastic leukemia
Blood,
March 1, 2007;
109(5):
2202 - 2204.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Lierman and J. Cools
ETV6 and PDGFRB: a license to fuse
Haematologica,
February 1, 2007;
92(2):
145 - 147.
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Xu, Q. Zhang, J. Luo, S. Xing, Q. Li, S. B. Krantz, X. Fu, and Z. J. Zhao
JAK2V617F: prevalence in a large Chinese hospital population
Blood,
January 1, 2007;
109(1):
339 - 342.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Kennedy, F. Barabe, B. J. Patterson, J. Bayani, J. A. Squire, D. L. Barber, and J. E. Dick
Expression of TEL-JAK2 in primary human hematopoietic cells drives erythropoietin-independent erythropoiesis and induces myelofibrosis in vivo
PNAS,
November 7, 2006;
103(45):
16930 - 16935.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. H. Kurzer, P. Saharinen, O. Silvennoinen, and C. Carter-Su
Binding of SH2-B Family Members within a Potential Negative Regulatory Region Maintains JAK2 in an Active State.
Mol. Cell. Biol.,
September 1, 2006;
26(17):
6381 - 6394.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. G. Rucker, L. Bullinger, C. Schwaenen, D. B. Lipka, S. Wessendorf, S. Frohling, M. Bentz, S. Miller, C. Scholl, R. F. Schlenk, et al.
Disclosure of Candidate Genes in Acute Myeloid Leukemia With Complex Karyotypes Using Microarray-Based Molecular Characterization
J. Clin. Oncol.,
August 20, 2006;
24(24):
3887 - 3894.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Walz, B. J. Crowley, H. E. Hudon, J. L. Gramlich, D. S. Neuberg, K. Podar, J. D. Griffin, and M. Sattler
Activated Jak2 with the V617F Point Mutation Promotes G1/S Phase Transition
J. Biol. Chem.,
June 30, 2006;
281(26):
18177 - 18183.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Mazurkiewicz-Munoz, L. S. Argetsinger, J.-L. K. Kouadio, A. Stensballe, O. N. Jensen, J. M. Cline, and C. Carter-Su
Phosphorylation of JAK2 at Serine 523: a Negative Regulator of JAK2 That Is Stimulated by Growth Hormone and Epidermal Growth Factor.
Mol. Cell. Biol.,
June 1, 2006;
26(11):
4052 - 4062.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. S. Lucet, E. Fantino, M. Styles, R. Bamert, O. Patel, S. E. Broughton, M. Walter, C. J. Burns, H. Treutlein, A. F. Wilks, et al.
The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor
Blood,
January 1, 2006;
107(1):
176 - 183.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Lu, R. Levine, W. Tong, G. Wernig, Y. Pikman, S. Zarnegar, D. G. Gilliland, and H. Lodish
Expression of a homodimeric type I cytokine receptor is required for JAK2V617F-mediated transformation
PNAS,
December 27, 2005;
102(52):
18962 - 18967.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Jelinek, Y. Oki, V. Gharibyan, C. Bueso-Ramos, J. T. Prchal, S. Verstovsek, M. Beran, E. Estey, H. M. Kantarjian, and J.-P. J. Issa
JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome-negative CML, and megakaryocytic leukemia
Blood,
November 15, 2005;
106(10):
3370 - 3373.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. L. Levine, M. Loriaux, B. J. P. Huntly, M. L. Loh, M. Beran, E. Stoffregen, R. Berger, J. J. Clark, S. G. Willis, K. T. Nguyen, et al.
The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia
Blood,
November 15, 2005;
106(10):
3377 - 3379.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Scott, P. J. Campbell, E. J. Baxter, T. Todd, P. Stephens, S. Edkins, R. Wooster, M. R. Stratton, P. A. Futreal, and A. R. Green
The V617F JAK2 mutation is uncommon in cancers and in myeloid malignancies other than the classic myeloproliferative disorders
Blood,
October 15, 2005;
106(8):
2920 - 2921.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. V. Jones, S. Kreil, K. Zoi, K. Waghorn, C. Curtis, L. Zhang, J. Score, R. Seear, A. J. Chase, F. H. Grand, et al.
Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders
Blood,
September 15, 2005;
106(6):
2162 - 2168.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Frohling, C. Scholl, D. G. Gilliland, and R. L. Levine
Genetics of Myeloid Malignancies: Pathogenetic and Clinical Implications
J. Clin. Oncol.,
September 10, 2005;
23(26):
6285 - 6295.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Nakamura, Y. Nakamura, K. Maki, Y. Sato, and K. Mitani
Cloning and Characterization of the Novel Chimeric Gene TEL/PTPRR in Acute Myelogenous Leukemia with inv(12)(p13q13)
Cancer Res.,
August 1, 2005;
65(15):
6612 - 6621.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Tefferi and D. G. Gilliland
The JAK2V617F Tyrosine Kinase Mutation in Myeloproliferative Disorders: Status Report and Immediate Implications for Disease Classification and Diagnosis
Mayo Clin. Proc.,
July 1, 2005;
80(7):
947 - 958.
[Abstract]
[PDF]
|
|
|
|
|
|
|
V. Moucadel and S. N. Constantinescu
Differential STAT5 Signaling by Ligand-dependent and Constitutively Active Cytokine Receptors
J. Biol. Chem.,
April 8, 2005;
280(14):
13364 - 13373.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Reiter, C. Walz, A. Watmore, C. Schoch, I. Blau, B. Schlegelberger, U. Berger, N. Telford, S. Aruliah, J. A. Yin, et al.
The t(8;9)(p22;p24) Is a Recurrent Abnormality in Chronic and Acute Leukemia that Fuses PCM1 to JAK2
Cancer Res.,
April 1, 2005;
65(7):
2662 - 2667.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Maeda, F. Yagasaki, M. Ishikawa, N. Takahashi, and M. Bessho
Transforming property of TEL-FGFR3 mediated through PI3-K in a T-cell lymphoma that subsequently progressed to AML
Blood,
March 1, 2005;
105(5):
2115 - 2123.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Wadleigh, D. J. DeAngelo, J. D. Griffin, and R. M. Stone
After chronic myelogenous leukemia: tyrosine kinase inhibitors in other hematologic malignancies
Blood,
January 1, 2005;
105(1):
22 - 30.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. W. Harder, C. Quilici, E. Naik, M. Inglese, N. Kountouri, A. Turner, K. Zlatic, D. M. Tarlinton, and M. L. Hibbs
Perturbed myelo/erythropoiesis in Lyn-deficient mice is similar to that in mice lacking the inhibitory phosphatases SHP-1 and SHIP-1
Blood,
December 15, 2004;
104(13):
3901 - 3910.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Schick, E. J. Oakeley, N. E. Hynes, and A. Badache
TEL/ETV6 Is a Signal Transducer and Activator of Transcription 3 (Stat3)-induced Repressor of Stat3 Activity
J. Biol. Chem.,
September 10, 2004;
279(37):
38787 - 38796.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. O. Flowers, H. M. Johnson, M. G. Mujtaba, M. R. Ellis, S. M. I. Haider, and P. S. Subramaniam
Characterization of a Peptide Inhibitor of Janus Kinase 2 That Mimics Suppressor of Cytokine Signaling 1 Function
J. Immunol.,
June 15, 2004;
172(12):
7510 - 7518.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. E. Tognon, C. D. Mackereth, A. M. Somasiri, L. P. McIntosh, and P. H. B. Sorensen
Mutations in the SAM Domain of the ETV6-NTRK3 Chimeric Tyrosine Kinase Block Polymerization and Transformation Activity
Mol. Cell. Biol.,
June 1, 2004;
24(11):
4636 - 4650.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. H. Kurzer, L. S. Argetsinger, Y.-J. Zhou, J.-L. K. Kouadio, J. J. O'Shea, and C. Carter-Su
Tyrosine 813 Is a Site of JAK2 Autophosphorylation Critical for Activation of JAK2 by SH2-B{beta}
Mol. Cell. Biol.,
May 15, 2004;
24(10):
4557 - 4570.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. J. Smith, E. Jacobson, S. Hamza, and H. Skelton
Unexplained Hypereosinophilia and the Need for Cytogenetic and Molecular Genetic Analyses
Arch Dermatol,
May 1, 2004;
140(5):
584 - 588.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. W. Sternberg and D. G. Gilliland
The Role of Signal Transducer and Activator of Transcription Factors in Leukemogenesis
J. Clin. Oncol.,
January 15, 2004;
22(2):
361 - 371.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Sattler, L. R. Quinnan, Y. B. Pride, J. L. Gramlich, S. C. Chu, G. C. Even, S.-K. Kraeft, L. B. Chen, and R. Salgia
2-Methoxyestradiol alters cell motility, migration, and adhesion
Blood,
July 1, 2003;
102(1):
289 - 296.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Benekli, M. R. Baer, H. Baumann, and M. Wetzler
Signal transducer and activator of transcription proteins in leukemias
Blood,
April 15, 2003;
101(8):
2940 - 2954.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Cools, D. J. DeAngelo, J. Gotlib, E. H. Stover, R. D. Legare, J. Cortes, J. Kutok, J. Clark, I. Galinsky, J. D. Griffin, et al.
A Tyrosine Kinase Created by Fusion of the PDGFRA and FIP1L1 Genes as a Therapeutic Target of Imatinib in Idiopathic Hypereosinophilic Syndrome
N. Engl. J. Med.,
March 27, 2003;
348(13):
1201 - 1214.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Ravandi, M. Talpaz, and Z. Estrov
Modulation of Cellular Signaling Pathways: Prospects for Targeted Therapy in Hematological Malignancies
Clin. Cancer Res.,
February 1, 2003;
9(2):
535 - 550.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Giordanetto and R. T. Kroemer
Prediction of the structure of human Janus kinase 2 (JAK2) comprising JAK homology domains 1 through 7
Protein Eng. Des. Sel.,
September 1, 2002;
15(9):
727 - 737.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M.-Y. Ho, M. H.-H. Nguyen, J. K. Dierov, K. M. Badger, B. K. Beattie, P. Tartaro, R. Haq, B. W. Zanke, M. P. Carroll, and D. L. Barber
TEL-JAK2 constitutively activates the extracellular signal-regulated kinase (ERK), stress-activated protein/Jun kinase (SAPK/JNK), and p38 signaling pathways
Blood,
July 30, 2002;
100(4):
1438 - 1448.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Li, J. C. Ruiz, and K. T. Chun
CUL-4A Is Critical for Early Embryonic Development
Mol. Cell. Biol.,
July 15, 2002;
22(14):
4997 - 5005.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Slupianek, G. Hoser, I. Majsterek, A. Bronisz, M. Malecki, J. Blasiak, R. Fishel, and T. Skorski
Fusion Tyrosine Kinases Induce Drug Resistance by Stimulation of Homology-Dependent Recombination Repair, Prolongation of G2/M Phase, and Protection from Apoptosis
Mol. Cell. Biol.,
June 15, 2002;
22(12):
4189 - 4201.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Cools, N. Mentens, M. D. Odero, P. Peeters, I. Wlodarska, M. Delforge, A. Hagemeijer, and P. Marynen
Evidence for position effects as a variant ETV6-mediated leukemogenic mechanism in myeloid leukemias with a t(4;12)(q11-q12;p13) or t(5;12)(q31;p13)
Blood,
March 1, 2002;
99(5):
1776 - 1784.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Onida, H. M. Kantarjian, T. L. Smith, G. Ball, M. J. Keating, E. H. Estey, A. B. Glassman, M. Albitar, M. I. Kwari, and M. Beran
Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients
Blood,
February 1, 2002;
99(3):
840 - 849.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Kelly, Q. Liu, J. L. Kutok, I. R. Williams, C. L. Boulton, and D. G. Gilliland
FLT3 internal tandem duplication mutations associated with human acute myeloid leukemias induce myeloproliferative disease in a murine bone marrow transplant model
Blood,
January 1, 2002;
99(1):
310 - 318.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Yagasaki, D. Wakao, Y. Yokoyama, Y. Uchida, I. Murohashi, H. Kayano, M. Taniwaki, A. Matsuda, and M. Bessho
Fusion of ETV6 to Fibroblast Growth Factor Receptor 3 in Peripheral T-Cell Lymphoma with a t(4;12)(p16;p13) Chromosomal Translocation
Cancer Res.,
December 1, 2001;
61(23):
8371 - 8374.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Schwaller, E. Anastasiadou, D. Cain, J. Kutok, S. Wojiski, I. R. Williams, R. LaStarza, B. Crescenzi, D. W. Sternberg, P. Andreasson, et al.
H4(D10S170), a gene frequently rearranged in papillary thyroid carcinoma, is fused to the platelet-derived growth factor receptor {beta} gene in atypical chronic myeloid leukemia with t(5;10)(q33;q22)
Blood,
June 15, 2001;
97(12):
3910 - 3918.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Frantsve, J. Schwaller, D. W. Sternberg, J. Kutok, and D. G. Gilliland
Socs-1 Inhibits TEL-JAK2-Mediated Transformation of Hematopoietic Cells through Inhibition of JAK2 Kinase Activity and Induction of Proteasome-Mediated Degradation
Mol. Cell. Biol.,
May 15, 2001;
21(10):
3547 - 3557.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K. Okuda, E. Weisberg, D. G. Gilliland, and J. D. Griffin
ARG tyrosine kinase activity is inhibited by STI571
Blood,
April 15, 2001;
97(8):
2440 - 2448.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. G. Gilliland
The Diverse Role of the ETS Family of Transcription Factors in Cancer: Commentary re: B. Davidson, Ets-1 Messenger RNA Expression Is a Novel Marker of Poor Survival in Ovarian Carcinoma. Clin. Cancer Res., 7: 551-557, 2001.
Clin. Cancer Res.,
March 1, 2001;
7(3):
451 - 453.
[Full Text]
|
|
|
|
|
|
|
Y. Kuno, A. Abe, N. Emi, M. Iida, T. Yokozawa, M. Towatari, M. Tanimoto, and H. Saito
Constitutive kinase activation of the TEL-Syk fusion gene in myelodysplastic syndrome with t(9;12)(q22;p12)
Blood,
February 15, 2001;
97(4):
1050 - 1055.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. R. Appelbaum, J. M. Rowe, J. Radich, and J. E. Dick
Acute Myeloid Leukemia
Hematology,
January 1, 2001;
2001(1):
62 - 86.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Buijs, L. van Rompaey, A. C. Molijn, J. N. Davis, A. C. O. Vertegaal, M. D. Potter, C. Adams, S. van Baal, E. C. Zwarthoff, M. F. Roussel, et al.
The MN1-TEL Fusion Protein, Encoded by the Translocation (12;22)(p13;q11) in Myeloid Leukemia, Is a Transcription Factor with Transforming Activity
Mol. Cell. Biol.,
December 15, 2000;
20(24):
9281 - 9293.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. J O'Shea, R. Visconti, T. P Cheng, and M. Gadina
Jaks and Stats as therapeutic targets
Ann Rheum Dis,
November 1, 2000;
59(90001):
i115 - 118.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Fenrick, L. Wang, J. Nip, J. M. Amann, R. J. Rooney, J. Walker-Daniels, H. C. Crawford, D. L. Hulboy, M. S. Kinch, L. M. Matrisian, et al.
TEL, a Putative Tumor Suppressor, Modulates Cell Growth and Cell Morphology of Ras-Transformed Cells While Repressing the Transcription of stromelysin-1
Mol. Cell. Biol.,
August 15, 2000;
20(16):
5828 - 5839.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. Kulkarni, C. Heath, S. Parker, A. Chase, S. Iqbal, C. F. Pocock, J. Kaeda, K. Cwynarski, J. M. Goldman, and N. C. P. Cross
Fusion of H4/D10S170 to the Platelet-derived Growth Factor Receptor {beta} in BCR-ABL-negative Myeloproliferative Disorders with a t(5;10)(q33;q21)
Cancer Res.,
July 1, 2000;
60(13):
3592 - 3598.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
C. Carron, F. Cormier, A. Janin, V. Lacronique, M. Giovannini, M.-T. Daniel, O. Bernard, and J. Ghysdael
TEL-JAK2 transgenic mice develop T-cell leukemia
Blood,
June 15, 2000;
95(12):
3891 - 3899.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Lacronique, A. Boureux, R. Monni, S. Dumon, M. Mauchauffe, P. Mayeux, F. Gouilleux, R. Berger, S. Gisselbrecht, J. Ghysdael, et al.
Transforming properties of chimeric TEL-JAK proteins in Ba/F3 cells
Blood,
March 15, 2000;
95(6):
2076 - 2083.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Iijima, T. Ito, T. Oikawa, M. Eguchi, M. Eguchi-Ishimae, N. Kamada, K. Kishi, S. Asano, Y. Sakaki, and Y. Sato
A new ETV6 / TEL partner gene, ARG (ABL-related gene or ABL2), identified in an AML-M3 cell line with a t(1;12)(q25;p13) translocation
Blood,
March 15, 2000;
95(6):
2126 - 2131.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kas, E. Finger, F. Grall, X. Gu, Y. Akbarali, J. Boltax, A. Weiss, P. Oettgen, R. Kapeller, and T. A. Libermann
ESE-3, a Novel Member of an Epithelium-specific Ets Transcription Factor Subfamily, Demonstrates Different Target Gene Specificity from ESE-1
J. Biol. Chem.,
January 28, 2000;
275(4):
2986 - 2998.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Ward, I. Touw, and A. Yoshimura
The Jak-Stat pathway in normal and perturbed hematopoiesis
Blood,
January 1, 2000;
95(1):
19 - 29.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Cazzaniga, S. Tosi, A. Aloisi, G. Giudici, M. Daniotti, P. Pioltelli, L. Kearney, and A. Biondi
The Tyrosine Kinase Abl-Related Gene ARG Is Fused to ETV6 in an AML-M4Eo Patient With a t(1;12)(q25;p13): Molecular Cloning of Both Reciprocal Transcripts
Blood,
December 15, 1999;
94(12):
4370 - 4373.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. P. Pollack, S. V. Kotenko, W. He, L. S. Izotova, B. L. Barnoski, and S. Pestka
The Human Homologue of the Yeast Proteins Skb1 and Hsl7p Interacts with Jak Kinases and Contains Protein Methyltransferase Activity
J. Biol. Chem.,
October 29, 1999;
274(44):
31531 - 31542.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. G. Lopez, C. Carron, C. Oury, P. Gardellin, O. Bernard, and J. Ghysdael
TEL Is a Sequence-specific Transcriptional Repressor
J. Biol. Chem.,
October 15, 1999;
274(42):
30132 - 30138.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Oettgen, K. Kas, A. Dube, X. Gu, F. Grall, U. Thamrongsak, Y. Akbarali, E. Finger, J. Boltax, G. Endress, et al.
Characterization of ESE-2, a Novel ESE-1-related Ets Transcription Factor That Is Restricted to Glandular Epithelium and Differentiated Keratinocytes
J. Biol. Chem.,
October 8, 1999;
274(41):
29439 - 29452.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Cools, C. Bilhou-Nabera, I. Wlodarska, C. Cabrol, P. Talmant, P. Bernard, A. Hagemeijer, and P. Marynen
Fusion of a Novel Gene, BTL, to ETV6 in Acute Myeloid Leukemias With a t(4;12)(q11-q12;p13)
Blood,
September 1, 1999;
94(5):
1820 - 1824.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. S. Ross and D. G. Gilliland
Transforming Properties of the Huntingtin Interacting Protein 1/ Platelet-derived Growth Factor beta Receptor Fusion Protein
J. Biol. Chem.,
August 6, 1999;
274(32):
22328 - 22336.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M.-Y. Ho, B. K. Beattie, J. A. Squire, D. A. Frank, and D. L. Barber
Fusion of the ets Transcription Factor TEL to Jak2 Results in Constitutive Jak-Stat Signaling
Blood,
June 15, 1999;
93(12):
4354 - 4364.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Y. Liu, C. Fan, R. Garcia, R. Jove, and K. S. Zuckerman
Constitutive Activation of the JAK2/STAT5 Signal Transduction Pathway Correlates With Growth Factor Independence of Megakaryocytic Leukemic Cell Lines
Blood,
April 1, 1999;
93(7):
2369 - 2379.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-B. Liu, T. Itoh, K.-i. Arai, and S. Watanabe
Constitutive Activation of JAK2 Confers Murine Interleukin-3-independent Survival and Proliferation of BA/F3 Cells
J. Biol. Chem.,
March 5, 1999;
274(10):
6342 - 6349.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Eguchi, M. Eguchi-Ishimae, A. Tojo, K. Morishita, K. Suzuki, Y. Sato, S. Kudoh, K. Tanaka, M. Setoyama, F. Nagamura, et al.
Fusion of ETV6 to Neurotrophin-3 Receptor TRKC in Acute Myeloid Leukemia With t(12;15)(p13;q25)
Blood,
February 15, 1999;
93(4):
1355 - 1363.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Chase, A. Reiter, L. Burci, G. Cazzaniga, A. Biondi, J. Pickard, I. A.G. Roberts, J. M. Goldman, and N. C.P. Cross
Fusion of ETV6 to the Caudal-Related Homeobox Gene CDX2 in Acute Myeloid Leukemia With the t(12;13)(p13;q12)
Blood,
February 1, 1999;
93(3):
1025 - 1031.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Corey and S. M. Anderson
Src-Related Protein Tyrosine Kinases in Hematopoiesis
Blood,
January 1, 1999;
93(1):
1 - 14.
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. N. Danial, J. A. Losman, T. Lu, N. Yip, K. Krishnan, J. Krolewski, S. P. Goff, J. Y. J. Wang, and P. B. Rothman
Direct Interaction of Jak1 and v-Abl Is Required for v-Abl-Induced Activation of STATs and Proliferation
Mol. Cell. Biol.,
November 1, 1998;
18(11):
6795 - 6804.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
B. P. Rubin, C.-J. Chen, T. W. Morgan, S. Xiao, H. E. Grier, H. P. Kozakewich, A. R. Perez-Atayde, and J. A. Fletcher
Congenital Mesoblastic Nephroma t(12;15) Is Associated with ETV6-NTRK3 Gene Fusion : Cytogenetic and Molecular Relationship to Congenital (Infantile)Fibrosarcoma
Am. J. Pathol.,
November 1, 1998;
153(5):
1451 - 1458.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Harrison, P. E. McCoon, R. Binari, M. Gilman, and N. Perrimon
Drosophila unpaired encodes a secreted protein that activates the JAK signaling pathway
Genes & Dev.,
October 15, 1998;
12(20):
3252 - 3263.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
C. M. Slupsky, L. N. Gentile, L. W. Donaldson, C. D. Mackereth, J. J. Seidel, B. J. Graves, and L. P. McIntosh
Structure of the Ets-1 pointed domain and mitogen-activated protein kinase phosphorylation site
PNAS,
October 13, 1998;
95(21):
12129 - 12134.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Reiter, J. Sohal, S. Kulkarni, A. Chase, D. H.C. Macdonald, R. C.T. Aguiar, C. Goncalves, J. M. Hernandez, B. A. Jennings, J. M. Goldman, et al.
Consistent Fusion of ZNF198 to the Fibroblast Growth Factor Receptor-1 in the t(8;13)(p11;q12) Myeloproliferative Syndrome
Blood,
September 1, 1998;
92(5):
1735 - 1742.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. C. Wang, W. Swat, Y. Fujiwara, L. Davidson, J. Visvader, F. Kuo, F. W. Alt, D. G. Gilliland, T. R. Golub, and S. H. Orkin
The TEL/ETV6 gene is required specifically for hematopoiesis in the bone marrow
Genes & Dev.,
August 1, 1998;
12(15):
2392 - 2402.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Onishi, T. Nosaka, K. Misawa, A. L.-F. Mui, D. Gorman, M. McMahon, A. Miyajima, and T. Kitamura
Identification and Characterization of a Constitutively Active STAT5 Mutant That Promotes Cell Proliferation
Mol. Cell. Biol.,
July 1, 1998;
18(7):
3871 - 3879.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
T. S. Ross, O. A. Bernard, R. Berger, and D. G. Gilliland
Fusion of Huntingtin Interacting Protein 1 to Platelet-Derived Growth Factor beta Receptor (PDGFbeta R) in Chronic Myelomonocytic Leukemia With t(5;7)(q33;q11.2)
Blood,
June 15, 1998;
91(12):
4419 - 4426.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Lacronique, A. Boureux, V. Della Valle, H. Poirel, C. T. Quang, M. Mauchauffé, C. Berthou, M. Lessard, R. Berger, J. Ghysdael, et al.
A TEL-JAK2 Fusion Protein with Constitutive Kinase Activity in Human Leukemia
Science,
November 14, 1997;
278(5341):
1309 - 1312.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
X. Gu, B.-H. Shin, Y. Akbarali, A. Weiss, J. Boltax, P. Oettgen, and T. A. Libermann
Tel-2 Is a Novel Transcriptional Repressor Related to the Ets Factor Tel/ETV-6
J. Biol. Chem.,
March 16, 2001;
276(12):
9421 - 9436.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kamizono, T. Hanada, H. Yasukawa, S. Minoguchi, R. Kato, M. Minoguchi, K. Hattori, S. Hatakeyama, M. Yada, S. Morita, et al.
The SOCS Box of SOCS-1 Accelerates Ubiquitin-dependent Proteolysis of TEL-JAK2
J. Biol. Chem.,
April 13, 2001;
276(16):
12530 - 12538.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H.-H. Nguyen, J. M.-Y. Ho, B. K. Beattie, and D. L. Barber
TEL-JAK2 Mediates Constitutive Activation of the Phosphatidylinositol 3'-Kinase/Protein Kinase B Signaling Pathway
J. Biol. Chem.,
August 24, 2001;
276(35):
32704 - 32713.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Sarkar, B. P. Pollack, K.-T. Lin, S. V. Kotenko, J. R. Cook, A. Lewis, and S. Pestka
hTid-1, a Human DnaJ Protein, Modulates the Interferon Signaling Pathway
J. Biol. Chem.,
December 21, 2001;
276(52):
49034 - 49042.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Salomon-Nguyen, V. Della-Valle, M. Mauchauffe, M. Busson-Le Coniat, J. Ghysdael, R. Berger, and O. A. Bernard
The t(1;12)(q21;p13) translocation of human acute myeloblastic leukemia results in a TEL-ARNT fusion
PNAS,
June 6, 2000;
97(12):
6757 - 6762.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
Abstract
Introduction
Abstract