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 Previous Article | Table of Contents | Next Article 
Blood, Vol. 92 No. 6 (September 15), 1998:
pp. 2118-2122
Acute Mixed Lineage Leukemia With an inv(8)(p11q13) Resulting in
Fusion of the Genes for MOZ and TIF2
By
Jian Liang,
Leonard Prouty,
B. Jill Williams,
Mark A. Dayton, and
Kerry L. Blanchard
From the Departments of Molecular Biology and Biochemistry,
Pediatrics, Urology, and Medicine, the Feist-Weiller Cancer Center,
Louisiana State University Medical School, Shreveport, LA.
 |
ABSTRACT |
Chromosomal abnormalities in acute leukemia have led to the
discovery of many genes involved in normal hematopoiesis and in malignant transformation. We have identified the fusion partners in an
inv(8)(p11q13) from a patient with acute mixed lineage leukemia. We
show by fluorescence in situ hybridization (FISH) analysis, Southern
blotting, and reverse transcriptase-polymerase chain reaction (RT-PCR)
that the genes for MOZ, monocytic leukemia
zinc finger protein, and TIF2,
transcriptional intermediary factor 2, are involved in the inv(8)(p11q13). We demonstrate that the inversion
creates a fusion between the 5 end of MOZ mRNA and the
3 end of TIF2 mRNA maintaining the translational frame
of the protein. The predicted fusion protein contains the zinc finger domains, the nuclear localization domains, the histone
acetyltransferase (HAT) domain, and a portion of the acidic domain of
MOZ, coupled to the CREB-binding protein (CBP)
interaction domain and the activation domains of TIF2. The
breakpoint is distinct from the breakpoint in the t(8;16)(p11;p13)
translocation in acute monocytic leukemia with erythrophagocytosis that
fuses MOZ with CBP. The reciprocal TIF2-MOZ fusion gene is not expressed, perhaps as a
result of a deletion near the chromosome 8 centromere. The
MOZ-TIF2 fusion is one of a new family of chromosomal
rearrangements that associate HAT activity, transcriptional
coactivation, and acute leukemia.
© 1998 by The American Society of Hematology.
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INTRODUCTION |
SPECIFIC RECURRING chromosomal
abnormalities are commonly associated with acute myeloid
leukemia.1 These chromosomal anomalies influence the
molecular and cellular phenotype of the leukemic blasts and may be
responsible for their malignant potential.2 The aberrations
often lead to the formation of one or more fusion genes resulting in
the overexpression or untimely expression of a normal gene, eg, the
MYC/Ig gene enhancer fusion produced by the t(8;14) in
Burkitt's lymphoma,3,4 or the creation of a new gene
product by fusing genes as in the PML-RAR fusion produced by
the t(15;17) characteristic of acute promyelocytic
leukemia.5,6 Some regions are common partners in fusion
events; 11q23 is involved in at least 40 different translocations in
acute leukemia.
Two distinct clinical syndromes have been associated with 8p11: a
chronic myeloproliferative disorder complicated by T-cell lymphoblastic
leukemia/lymphoma and peripheral blood eosinophilia and a M4/M5 acute
monocytic leukemia with prominent erythrophagocytosis.7-11 The t(8;16) translocation in acute monocytic leukemia with
erythrophagocytosis fuses the gene for MOZ with the
transcriptional coactivator CBP.10 The t(8;13)
translocation associated with a chronic myeloproliferative disorder,
lymphoblastic lymphoma, and eosinophilia juxtaposes the gene for
FGFR1 with a novel gene that encodes the zinc finger protein,
ZNF198.12 These translocations appear
to involve different portions of 8p11 than the t(8;22) translocation
observed in acute monocytic leukemia.8
We have identified the genes involved in a novel fusion event in a case
of acute mixed-lineage leukemia associated with an inv(8)(p11q13). The
patient's clinical presentation is distinct from the
myeloproliferative/lymphoblastic disorder and the M4/M5 leukemia with
erythrophagocytosis previously associated with 8p11 abnormalities, and
the fusion event creates a chimeric gene from the potential histone
transacetylase, MOZ, and the transcriptional coactivator,
TIF2.
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MATERIALS AND METHODS |
Patient.
A 29-year-old female presented after 1 month of back pain, 2 weeks of
extensive bruising, and a few hours of rectal bleeding. She had 102,000 blasts/µL that were French-American-British (FAB) M0/M1 by
morphology; M7 by histochemical staining; positive for CD5, CD10,
HLA-DR, and CD33; and negative for CD34, CD19, CD13, and CD7.
Cytogenetic analysis of bone marrow cells showed that 3 cells were 46, XX and that 17 cells were inv(8)(p11q13), der(10) t(1;10)(q25;p15)
(Fig 1A). The patient was enrolled and
treated on SWOG study 9034, but relapsed 30 days after induction.
Remission was attained after allogeneic bone marrow transplantation,
but 67 days after transplantation she presented with headaches.
Stereotactic biopsy of her brain lesion showed a chloroma and, despite
cranial irradiation, she suffered intraparenchymal cerebellar
hemorrhage and died.
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| Fig 1.
EBV-LEUK1 cytogenetics and FISH analyses. (A) A partial
karyotype of G-banded chromosomes 1, 8, and 10 from EBV-LEUK1 cells.
The arrows indicate regions of chromosomal fusion. (B) Map of the YACs
versus genetic markers from singly linked contigs WC-8.6 and WC-8.7.
The relative size of the YACs and the spacing of the markers are not
drawn to scale and are not precisely known. (C) Examples of FISH
performed on EBV-LEUK1 cells with YAC probes from the human CEPH
library. YACs 806_e_9, 857_g_5, and 971_c_5 appear yellow-green. The
chromosome 8 centromeric probe appears red. YAC 911_f_10 and the 8q24
probe (MYC) appear red and yellow, respectively. DAPI-stained
chromosomes are blue. White arrows highlight the split signal obtained
with YAC 857_g_5, and yellow arrows highlight the lack of binding to
911_f_10.
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Epstein-Barr virus (EBV)-transformed cell line.
Frozen primary leukemic blasts (LEUK1) were infected with EBV and grown
without cyclosporin A. Two months after infection, one culture
(EBV-LEUK1) began active proliferation. Cytogenetic analysis of
EBV-LEUK1 showed an inv(8)(p11q13) and a der(10)t(1;10)(q25;p15) in all
metaphases. Flow cytometric analysis of EBV-LEUK1 showed loss of the
CD10 and gain of CD7. The cells were also positive for CD33, CD13, and
CD41.
Fluorescence in situ hybridization (FISH).
EBV-LEUK1 metaphase spreads were prepared after cell cycle
synchronization, inhibition of chromosome condensation, and metaphase arrest with colcemid. Total yeast DNA was isolated by the spheroplast method from yeast artificial chromosome (YAC) clones from the human
CEPH library (Research Genetics, Inc, Huntsville, AL).
Human DNA was labeled with biotin or digoxigenin (1:3 ratio to dT;
Boehringer Mannheim, Indianapolis, IN) by
Alu-polymerase chain reaction (PCR) with Alu primers
CL1 and CL2 (Table 1). Probes were combined with human cot-1 DNA in Hybrisol VII (Oncor,
Gaithersburg, MD) before hybridization and detected with
Cy3-streptavidin (Jackson ImmunoResearch, West Grove, PA), fluorescein
isothiocyanate (FITC)-avidin (Oncor),
FITC-antidigoxigenin, or rhodamine-antidigoxigenin (Oncor). Chromosomes
were stained with 4,6-diamidino-2-phenylindole (DAPI).
Southern blot analysis.
DNA from LEUK1 cells and normal peripheral blood mononuclear cells was
digested with restriction enzymes, size-fractionated, and transferred
to Nytran Plus membranes (Schleicher & Schuell, Keene,
NH). A MOZ probe generated by PCR (MOZ
2549F to 3663R) was labeled with  -32P-dCTP by random
priming. After hybridization and stringent washing, the blot was
exposed to a phosphorimager screen.
Reverse transcriptase-PCR (RT-PCR).
EBV-LEUK1 cells were lysed with guanidinium thiocyanate. After
homogenization, total cellular RNA was collected through 5.7 mol/L
CsCl. Total cellular RNA (0.5 µg) was denatured at 75°C for 5 minutes with 50 pmol of random hexamers. First-strand cDNA was
prepared in a 20 µL reaction containing 2.5 U of Moloney's murine
leukemia virus (MMLV) reverse transcriptase (Superscript RT; GIBCO BRL, Gaithersburg, MD), 20 mmol/L Tris-HCl, pH
7.5, 50 mmol/L KCl, 10 mmol/L MgCl2, 2.5 mmol/L
dithiothreitol, 0.5 U RNasin (Promega, Madison, WI), and
625 µmol/L of each dNTP. Twenty-microliter PCR reactions, containing
5 pmol each of MOZ and/or TIF2 primers, 0.2 mmol/L dNTPs, 1× Vent buffer, 0.5 U Taq (Fisher, Pittsburgh,
PA), and 0.2 U Vent (New England Biolabs, Beverly,
MA) DNA polymerase, were incubated at 94°C for 10 seconds, 55°C for 30 seconds, and 72°C for 4 minutes for 10 cycles, followed by 25 cycles with a 20-second increase in elongation
time/cycle.
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RESULTS |
FISH.
A map showing the relative positions of YACs is presented (Fig 1B). YAC
probes from contigs WC-8.5, WC-8.6, and WC-8.7 (Whitehead Institute, Cambridge, MA) were hybridized to chromosome
spreads from EBV-LEUK1. Chromosome 8 was identified by hybridization
with a chromosome 8 centromere probe or a probe containing MYC
(YAC 934_e_1, band 8q24). YAC 806_e_9 from contig WC-8.6 is telomeric to the breakpoint on the p-arm and appears more telomeric on the inv(8)
chromosome than on the normal chromosome 8. YAC 857_g_5 hybridizes as a split signal on the inv(8) chromosome (Fig 1C). The
telomeric end of YAC 857_g_5 completely overlaps YAC 829_d_12, which
contains the gene for MOZ.9,10 YAC 971_c_5 is
adjacent to the centromere on 8p, but becomes pericentrometic after the paracentric inversion. YAC 911_f_10 from contig WC-8.7 is
pericentromeric on the wild-type chromosome, but absent from the inv(8)
chromosome. The lack of a hybridization signal for YAC 911_f_10
suggests the inv(8) contains a deletion near the centromere (Fig 1C).
Southern blot analysis for MOZ.
The involvement of MOZ in the breakpoint at 8p11 is supported
by Southern blot analysis of DNA from primary leukemic cells (Fig 2). A MOZ cDNA probe detects
rearranged fragments of 3.5, 8.0, and 15 kb after digestion with Bgl 2, Hind 3, and Stu 1 (Fig 2, lanes 4, 1, and 8), respectively. Hind 3 and
Stu 1 restriction fragment length polymorphisms were identified in DNA
from normal control no. 1 (Fig 2, lanes 2 and 9).
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| Fig 2.
Southern blot analysis of LEUK1 and normal control DNA
probed with a MOZ cDNA probe. High molecular weight DNA was
digested to completion with Hind 3, Bgl 2, or Stu 1; size-fractionated;
blotted; and hybridized to a probe that extends from bp 2549 to 3663 in
the MOZ cDNA. The blot was washed in 0.1× SSC at 65°C for
30 minutes. Lanes 1, 4, and 8 contain DNA from LEUK1 cells; lanes 2, 5, and 9 contain DNA from normal volunteer no. 1; lanes 3, 6, and 10 contain DNA from normal volunteer no. 2; and lanes 7 and 11 contain DNA
from normal volunteer no. 3. The arrows indicate the positions of the
rearranged restriction fragments in LEUK1 DNA. Normal volunteer no. 1 has restriction fragment length polymorphisms after Hind 3 and Stu 1 digestion (lanes 2 and 9).
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Identification of the fusion partner.
During our analysis of the MOZ fusion partner by rapid
amplification of cDNA ends (RACE), a fusion of
MOZ to a gene on 8q13 was reported in a case of acute monocytic
leukemia.13 In this case, MOZ was fused to the gene
for TIF2. The presence of a fusion between MOZ and
TIF2 in EBV-LEUK1 cells was tested by RT-PCR. Five antisense
primers evenly spaced across the coding sequence of TIF2 were
paired with 3 sense primers derived from MOZ (Table 1). TIF
3308R, when combined with MOZ primers 1606F, 2549F, and 3304F,
supported the amplification of PCR products of approximately 2,470, 1,530, and 775 bp (Fig 3, lanes 5, 10, and
15), suggesting that the breakpoint is flanked by MOZ 3304F and TIF
3308R. None of the TIF2 primers derived from sequence 5
of TIF 3308R resulted in successful amplification when paired with
MOZ primers.
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| Fig 3.
RT-PCR of LEUK1 RNA with MOZ and TIF2
primers. cDNA from EBV-LEUK1 was amplified by PCR, and products were
subjected to electrophoresis in 2% agarose gels in 1× TAE. Three
sense primers from MOZ were paired with 5 antisense primers
from TIF2. Specific PCR products were produced when each
MOZ primer was combined with TIF 3308R (lanes 5, 10, and 15).
The M2 indicates  -BstE 2 DNA size markers.
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Expression of wild-type MOZ and TIF2 by RT-PCR.
We queried whether wild-type MOZ and TIF2 are expressed
in EBV-LEUK1 cells. Amplification with primers that flank the
MOZ breakpoint (MOZ 3303F v MOZ 3784R and MOZ 3880R)
generated PCR products of 482 and 578 bp with cDNA prepared from normal
peripheral blood mononuclear (Fig 4A, lanes
1 and 2) and EBV-LEUK1 cells (Fig 4A, lanes 3 and 4). Appropriately
sized products (1,316 bp/1,109 bp) were also obtained with primers that
flank the TIF2 breakpoint, TIF 1993F and TIF 3308R (Fig 4B).
This region of TIF2 contains a 207-bp alternatively spliced
exon, giving rise to two PCR products.
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| Fig 4.
Expression of wild-type MOZ and TIF2. (A)
RNA from EBV-LEUK1 and normal peripheral blood mononuclear cells was
analyzed by RT-PCR. A PCR product containing the MOZ breakpoint
was amplified when MOZ 3303F was paired with either MOZ 3784R (lanes 1 and 3) or MOZ 3880R (lanes 2 and 4). (B) TIF2 primers that
flank the TIF2 breakpoint amplify products of 1,315 and 1,105 bp from EBV-LEUK1 cDNA, corresponding to the alternatively spliced
forms of TIF2 cDNA. M1 and M2 indicate 100-bp marker ladders
and -BstE 2 DNA size markers, respectively.
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Expression of the TIF2-MOZ fusion.
The chromosomal inversion that created the MOZ-TIF2
fusion at 8p11 must result in a reciprocal genomic fusion at 8q13. The expression of a TIF2-MOZ fusion mRNA in EBV-LEUK1 was
tested with sense primers 5 of the TIF2 breakpoint and
antisense primers 3 of the MOZ breakpoint. No PCR
products were generated with these primers, suggesting that the
reciprocal fusion mRNA is not expressed (data not shown).
Identification of the breakpoint.
The PCR product obtained from EBV-LEUK1 cDNA with MOZ 2549F and
TIF2 4939R primers was subjected to DNA sequencing. The
breakpoint between the cDNAs for TIF2 and MOZ occurs at
bp 2974 and 3744, respectively (Fig 5A).
The breakpoint creates an in-frame fusion of MOZ and
TIF2 at amino acids 1117 and 939, respectively (Fig 5B).
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| Fig 5.
DNA sequence across the breakpoint. An RT-PCR product
from EBV-LEUK1 RNA that extends from MOZ 2549F to TIF2 4939R was
subcloned. (A) The subcloned DNA was sequenced with primer TIF2 3308R.
The arrow indicates the breakpoint between MOZ and TIF2
at nucleotides 2974 and 3744, respectively. (B) The DNA sequence around
the breakpoint and the predicted amino acid sequence is
presented.
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DISCUSSION |
Clinical syndromes with 8p11 abnormalities include a chronic
myeloproliferative disorder associated with T-cell lymphoblastic lymphoma and eosinophilia [t(8;13)(p11;q11-12), t(8;9)(p11;q34), t(6;8)(q27;p11)]7,8,11 and an acute myelomonocytic
leukemia with erythrophagocytosis [t(8;16)(p11;p13), inv(8)(p11q13),
t(8;22)(p11;q13), and t(8;19)(p11;q13)].10,14,15 Two genes
from the 8p11 locus have been identified in these diseases: MOZ, isolated by positional cloning of the breakpoint in
t(8;16),10 and FGFR1, cloned as the chromosome 8 contribution to the t(8;13).12 The 8p11 genes are fused to
CBP and ZNF198, respectively. ZNF198 provides a
zinc finger dimerization motif to the tyrosine kinase domain of
FGFR1, creating a fusion protein that is predominantly cytoplasmic and probably constitutively activated by
homodimerization.12 Both MOZ10,16 and
CBP17-19 have been associated with chromatin
remodeling and implicated in histone acetylation.
We have identified a gene fusion created by an inv(8)(p11q13) in a case
of de novo acute mixed lineage leukemia. The 8p11 gene encodes
MOZ, a 2,004 amino acid protein with 2 types of zinc fingers
and a HAT signature motif,10 and the 8q13 gene encodes TIF2, a transcriptional coactivator with nuclear receptor
binding domains, a CBP interaction domain and two activation
domains.20,21 The fusion gene produces a mRNA containing
the 5 end of MOZ appended in translational frame to the
3 end of TIF2. The breakpoints occur at nucleotide 3744 of MOZ (corresponding to amino acid 1117) and 2974 of
TIF2 (corresponding to amino acid 939). The inv(8) MOZ
breakpoint is distinct from the breakpoint in the MOZ-CBP fusion in the t(8;16)(p11;p13) (nucleotide 5033, amino acid
1547).10 The fusion product retains the C4HC3 and C2HC zinc
fingers, two putative nuclear localization signals, the HAT domain, the
MYST domain and a portion of the acidic domain of MOZ, and the
CBP interaction domain, the Q-rich region, and two activation
domains of TIF2 (Fig 6). The
breakpoint in TIF2 occurs at the splice acceptor site for an
alternatively spliced exon,20 suggesting that the genomic
breakpoint is within an intron. We have verified expression of
wild-type MOZ and two known variants of TIF2 in
EBV-LEUK1 cells by amplifying cDNA with primers that flank either the
MOZ or the TIF2 breakpoint. The TIF2-MOZ
reciprocal fusion is not expressed at the sensitivity of RT-PCR,
perhaps due to loss of genetic material from the promoter or N-terminal
coding region of TIF2. If the genomic deletion on the inv(8)
chromosome involves TIF2, the C-terminal portion of MOZ
may have joined with an unknown gene adjacent to TIF2; hence,
the possibility of an expressed reciprocal fusion has not been entirely
eliminated.
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| Fig 6.
The MOZ, TIF2, and MOZ-TIF2
fusion proteins. The protein domains of MOZ, TIF2, and
the MOZ-TIF2 fusion are presented. C4HC3, zinc finger domain
associated with chromatin binding; C2HC, zinc finger domain associated
with HAT activity; HAT, histone acetyltransferase; NLS, nuclear
localization signals; MYST, MOZ, YBF2, SAS2,
and Tip60 homology region; inv(8), breakpoint in acute mixed
lineage leukemia; Acidic, acidic domain; t(8;16), breakpoint in AML
with erythrophagocytosis; P/G, proline/glutamine-rich region; MET,
methionine-rich region; bHLH, basic helix-loop-helix region; PAS,
Per/ARNT/Sim homology region; Alt.exon, alternatively spliced
exon (AA 869 to 938); AD2, activation domain-2; CID, CBP
interaction domain (contains activation domain-1); NID, nuclear hormone
receptor interaction domain; Q-rich, glutamine-rich region. The numbers
below each schematic correspond to amino acids.
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The involvement of MOZ, CBP, and TIF2 in acute
leukemia suggests that yet another class of cellular processes can be
deranged by gene fusion events. Each of these proteins possesses or
recruits HATs to chromatin. The ability of HATs to affect chromatin
structure and regulate gene expression is well
appreciated.22 How the MOZ-TIF2 fusion
protein is involved in acute leukemia is not known. We speculate that
the TIF2 portion of the fusion associates with CBP
providing additional activation domains for stimulating transcription or additional HAT activity for remodeling chromatin. The
protein-protein dimerization faces of MOZ could deliver the
CBP interaction domain and the activation domains of
TIF2 to unique chromosomal locations, modifying transcription
by allowing binding of CBP or other proteins. The fusion
protein could function as a dominant negative by interacting with
normal MOZ, TIF2, and/or CBP on or off
the surface of chromatin. We hope the discovery of the
MOZ-TIF2 fusion will uncover basic relationships
between the control of chromatin condensation and gene expression in
acute leukemia and suggest new targets for directed therapeutic
intervention.
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FOOTNOTES |
Submitted March 25, 1998;
accepted May 15, 1998.
Address reprint requests to Kerry L. Blanchard, PhD, MD, Louisiana
State University Medical Center, 1501 Kings Hwy, Shreveport, LA 71103;
e-mail: Kblanc{at}lsumc.edu.
The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" is accordance with 18 U.S.C. section 1734 solely to indicate this fact.
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REFERENCES |
1.
Mrozek K,
Heinonen K,
de la Chapelle A,
Bloomfield CD:
Clinical significance of cytogenetics in acute myeloid leukemia.
Semin Oncol
24:17,
1997[Medline]
[Order article via Infotrieve]
2.
Caligiuri MA,
Strout MP,
Gilliland DG:
Molecular biology of acute myeloid leukemia.
Semin Oncol
24:32,
1997[Medline]
[Order article via Infotrieve]
3.
Croce CM,
Nowell PC:
Molecular genetics of human B cell neoplasia.
Adv Immunol
38:245,
1986[Medline]
[Order article via Infotrieve]
4.
Thandla S,
Aplan PD:
Molecular biology of acute lymphocytic leukemia.
Semin Oncol
24:45,
1997[Medline]
[Order article via Infotrieve]
5.
Kakizuka A,
Miller WH Jr,
Umesono K,
Warrell RP Jr,
Frankel SR,
Murty VV,
Dmitrovsky E,
Evans RM:
Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR- with a novel putative transcription factor, PML.
Cell
66:663,
1991[Medline]
[Order article via Infotrieve]
6.
de The H,
Lavau C,
Marchio A,
Chomienne C,
Degos L,
Dejean A:
The PML-RAR- fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR.
Cell
66:675,
1991[Medline]
[Order article via Infotrieve]
7.
Inhorn RC,
Aster JC,
Roach SA,
Slapak CA,
Soiffer R,
Tantravahi R,
Stone RM:
A syndrome of lymphoblastic lymphoma, eosinophilia, and myeloid hyperplasia/malignancy associated with t(8;13)(p11;q11): Description of a distinctive clinicopathologic entity [see comments].
Blood
85:1881,
1995[Abstract/Free Full Text]
8.
Still IH,
Chernova O,
Hurd D,
Stone RM,
Cowell JK:
Molecular characterization of the t(8;13)(p11;q12) translocation associated with an atypical myeloproliferative disorder: Evidence for three discrete loci involved in myeloid leukemias on 8p11.
Blood
90:3136,
1997[Abstract/Free Full Text]
9.
Aguiar RC,
Chase A,
Coulthard S,
Macdonald DH,
Carapeti M,
Reiter A,
Sohal J,
Lennard A,
Goldman JM,
Cross NC:
Abnormalities of chromosome band 8p11 in leukemia: Two clinical syndromes can be distinguished on the basis of MOZ involvement.
Blood
90:3130,
1997[Abstract/Free Full Text]
10.
Borrow J,
Stanton VP Jr,
Andresen JM,
Becher R,
Behm FG,
Chaganti RS,
Civin CI,
Disteche C,
Dube I,
Frischauf AM,
Horsman D,
Mitelman F,
Volinia S,
Watmore AE,
Housman DE:
The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein [see comments].
Nat Genet
14:33,
1996[Medline]
[Order article via Infotrieve]
11.
Macdonald D,
Aguiar RC,
Mason PJ,
Goldman JM,
Cross NC:
A new myeloproliferative disorder associated with chromosomal translocations involving 8p11: A review [see comments].
Leukemia
9:1628,
1995[Medline]
[Order article via Infotrieve]
12.
Xiao S,
Nalabolu SR,
Aster JC,
Ma J,
Abruzzo L,
Jaffe ES,
Stone R,
Weissman SM,
Hudson TJ,
Fletcher JA:
FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukemia/lymphoma syndrome.
Nat Genet
18:84,
1998[Medline]
[Order article via Infotrieve]
13. (abstr, suppl 1)
Carapeti M,
Aguiar RCT,
Goldman JM,
Cross NCP:
A novel fusion between MOZ and the nuclear receptor coactivator TIF2 in AML with the inv(8)(p11q13).
Blood
90:318a,
1997
14.
Lai JL,
Zandecki M,
Fenaux P,
Preudhomme C,
Facon T,
Deminatti M:
Acute monocytic leukemia with (8;22)(p11;q13) translocation. Involvement of 8p11 as in classical t(8;16)(p11;p13).
Cancer Genet Cytogenet
60:180,
1992[Medline]
[Order article via Infotrieve]
15.
Stark B,
Resnitzky P,
Jeison M,
Luria D,
Blau O,
Avigad S,
Shaft D,
Kodman Y,
Gobuzov R,
Ash S,
Stein J,
Yaniv I,
Barak Y,
Zaivov R:
A distinct subtype of M4/M5 acute myeloblastic leukemia (AML) associated with t(8;16)(p11;p13), in a patient with the variant t(8;19)(p11;q13) Case report and review of the literature.
Leuk Res
19:367,
1995[Medline]
[Order article via Infotrieve]
16. (erratum 16:109, 1997)
Reifsnyder C,
Lowell J,
Clarke A,
Pillus L:
Yeast SAS silencing genes and human genes associated with AML and HIV-1 Tat interactions are homologous with acetyltransferases [see comments].
Nat Genet
14:42,
1996[Medline]
[Order article via Infotrieve]
17.
Sobulo OM,
Borrow J,
Tomek R,
Reshmi S,
Harden A,
Schlegelberger B,
Housman D,
Doggett NA,
Rowley JD,
Zeleznik-Le NJ:
MLL is fused to CBP, a histone acetyltransferase, in therapy-related acute myeloid leukemia with a t(11;16)(q23;p13.3).
Proc Natl Acad Sci USA
94:8732,
1997[Abstract/Free Full Text]
18.
Bannister AJ,
Kouzarides T:
The CBP co-activator is a histone acetyltransferase.
Nature
384:641,
1996[Medline]
[Order article via Infotrieve]
19.
Ogryzko VV,
Schiltz RL,
Russanova V,
Howard BH,
Nakatani Y:
The transcriptional coactivators p300 and CBP are histone acetyltransferases.
Cell
87:953,
1996[Medline]
[Order article via Infotrieve]
20.
Voegel JJ,
Heine MJ,
Zechel C,
Chambon P,
Gronemeyer H:
TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors.
EMBO J
15:3667,
1996[Medline]
[Order article via Infotrieve]
21.
Voegel JJ,
Heine MJ,
Tini M,
Vivat V,
Chambon P,
Gronemeyer H:
The coactivator TIF2 contains three nuclear receptor-binding motifs and mediates transactivation through CBP binding-dependent and -independent pathways.
EMBO J
17:507,
1998[Medline]
[Order article via Infotrieve]
22.
Brownell JE,
Allis CD:
Special HATs for special occasions: Linking histone acetylation to chromatin assembly and gene activation.
Curr Opin Genet Dev
6:176,
1996[Medline]
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Abstract
Introduction
Abstract