SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on October 10, 2002; DOI 10.1182/blood-2002-05-1474. This Article Abstract Full Text (PDF) All Versions of this Article: 2002-05-1474v1 101/4/1277    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Roumier, C. Articles by Preudhomme, C. Search for Related Content PubMed PubMed Citation Articles by Roumier, C. Articles by Preudhomme, C. Related Collections Neoplasia Brief Reports Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 February 2003, Vol. 101, No. 4, pp. 1277-1283 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Brief report M0 AML, clinical and biologic features of the disease, including AML1 gene mutations: a report of 59 cases by the Groupe Français d'Hématologie Cellulaire (GFHC) and the Groupe Français de Cytogénétique Hématologique (GFCH) Christophe Roumier, Virginie Eclache, Michelle Imbert, Frederic Davi, Elizabeth MacIntyre, Richard Garand, Pascaline Talmant, Pascale Lepelley, Jean Luc Lai, Olivier Casasnovas, Marc Maynadie, Francine Mugneret, Chrystele Bilhou-Naberra, Françoise Valensi, Isabelle Radford, Marie Joëlle Mozziconacci, Christine Arnoulet, Eliane Duchayne, Nicole Dastugue, Pascale Cornillet, Sylvie Daliphard, Francine Garnache, Najiba Boudjerra, Helene Jouault, Odile Fenneteau, Béatrice Pedron, Roland Berger, Georges Flandrin, Pierre Fenaux, and Claude Preudhomme From the Laboratoire d'Hématologie A, Laboratoire de Cytogénétique, and Service des Maladies du Sang, CHU Lille; Unité INSERM 524, Institut de Recherche sur le Cancer de Lille; Laboratoire d' Hématologie, Hôpital Jean Verdier, Bondy, Assistance Publique Hôpitaux de Paris; Hématologie Biologique and Hématologie Clinique, Hôpital Henri Mondor, Assistance Publique Hôpitaux de Paris; Hématologie clinique, Hôpital Pitié Salpetrière, Assistance Publique Hôpitaux de Paris; Hématologie Biologique, Hôpital Necker, Assistance Publique Hôpitaux de Paris; Laboratoire d'Hématologie and Cytogénétique Hématologique, Institut de Biologie, CHU Nantes; Unité d'hématologie Clinique, Service d'hématologie biologique, and Laboratoire de Cytogénétique, CHU Dijon; Laboratoire d'Hématologie, CHU Bordeaux; Laboratoire de Cytogénétique Hôpital Necker, Assistance Publique Hôpitaux de Paris; Laboratoire d'Hématologie Moléculaire et Cytogénétique, Institut Paoli Calmette, Marseille; Laboratoire d'hématologie and Laboratoire de Génétique des Hémopathies, Hôpital Purpan, Toulouse; Laboratoire d'Hématologie et de Cytogénétique, CH Reims; Laboratoire d'Hématologie, Etablissement de Transfusion Sanguine de Franche Comte; Service d'Hématologie, Centre Hospitalier Alger; Hématologie Biologique and Immunologie Biologique, Hôpital Robert Debre, Assistance Publique Hôpitaux de Paris; Unité INSERM 301, IGM, Hôpital Saint Louis Paris, France.     Abstract Top Abstract Introduction Study design Results and discussion References Mutations of the AML1 gene are frequent molecular abnormalities in minimally differentiated acute myeloblastic leukemia (M0 AML), a rare type of AML. In this retrospective multicenter study, morphologic, immunophenotypical, cytogenetic, and molecular features of 59 de novo M0 AML cases were analyzed and correlated to AML1 mutations. Point mutations of AML1 gene were observed in 16 cases (27%). They were correlated with higher white blood cell (WBC) count (P = .001), greater marrow blast involvement (P = .03), higher incidence of immunoglobulin H/T-cell receptor (IgH/TCR) gene rearrangement (P < .0001), and with a borderline significant lower incidence of complex karyotypes. In the 59 patients, FLT3 mutations were the only significant prognostic factors associated with short survival. (Blood. 2003;101:1277-1283) © 2003 by The American Society of Hematology.     Introduction Top Abstract Introduction Study design Results and discussion References Minimally differentiated acute myeloblastic leukemia (AML), now classified as M0 AML, is a rare type of AML associated with poor prognosis.1,2 Recently, we and others reported in M0 AML a high frequency of mutations of AML1 gene, a gene that plays a pivotal role in myeloid differentiation.3-6 In this multicenter cooperative work, we analyzed clinical and biologic characteristics of a large series of M0 AML and compared, in particular, patients with and without AML1 mutation.     Study design Top Abstract Introduction Study design Results and discussion References Patient population Fifty-nine patients diagnosed as de novo M0 AML between 1993 and 2000 in the hematology departments of 9 French university hospitals (Besançon, Bordeaux, Dijon, Lille, Marseille, Nantes, Paris, Reims, and Toulouse) were included. All cases were centrally reviewed by members of Groupe Français d'Hématologie Cellulaire (GFHC) for cytology, cytochemistry, and immunophenotyping and by members of Groupe Français de Cytogénétique Hématologique (GFCH) for cytogenetic findings. Patients with older age and/or poor clinical condition received supportive care only or moderate chemotherapy (Table 1). Other patients received anthracycline-AraC induction chemotherapy, based on European or French multicenter protocols for AML (acute Leukaemia French Association [ALFA], Bordeaux Grenoble Montpellier Toulouse [BGMT], European Organisation for Research and Treatment of Cancer [EORTC], and Groupe ouest des Leucemies et Autres Maladies du Sang [GOELAMS] cooperative groups).7-10 Patients who achieved complete remission (CR) received consolidation with high-dose AraC-based chemotherapy and autologous or allogeneic stem cell transplantation, depending on age, donor availability, and trial design.                                View this table: [in this window] [in a new window]   Table 1. Biological and clinical data Morphologic studies Bone marrow and peripheral blood smears were stained by May-Grünwald-Giemsa. Myeloperoxidase, naphthol AS-D-acetate esterases with and without fluoride inhibition, or naphthyl acetate butyrate esterases cytochemical reactions were performed. Immunophenotypic studies Immunophenotyping was performed by flow cytometry. Membrane expression of CD2, 3, 5, 7, 10, 19, 20, 22, 24, 79a, 34, 13, 33, 117, 14, 15, 41, 61, 65, and HLA-DR was tested. For CD3, CD13, CD22, and myeloperoxidase (MPO), intracytoplasmic antigen expression was also tested. Diagnostic criteria of M0 AML were (1) less than 3% myeloperoxidase-positive blasts; (2) expression of at least one of the following myeloid markers: CD13, CD33, or MPO; and (3) no expression of lymphoid markers except CD4 or CD7 (European Group for the Immunological Characterization of Leukemias [EGIL] criteria).11 Cytogenetic and fluorescence in situ hybridization (FISH) studies For conventional cytogenetic analysis, chromosomes were identified by R-bands by heating using Giemsa (RHG) and/or G-bands with trypsin using Giemsa (GTG) banding, and abnormalities were described according to International System for Cytogenetic Nomenclature (ISCN).12 FISH was performed according to standard methods and manufacturer's instructions by using whole chromosomes or locus-specific probe mixed lineage lymphoma (MLL), AML1 (Vysis, Downers Grove, IL), and yeast artificial chromosomes (YACs) probes for ALL1 fused gene from chromosome 10 (AF10), clathrin assembly lymphoid-myeloid leukemia (CALM), and ETS variant gene 6 (ETV6) regions obtained from the CENTRE d'Étude du Polymorphisme humain (CEPH; Paris, France) (815c7, 814d9, 936e2 YAC clones). Molecular studies Detection of AML1 mutations was made on DNA and/or cDNA from bone marrow cells, as previously reported.3,6 Study of FLT3 duplication, IgH (FR1, FR3, DJ), TCR- (Vg 1Vg 11; J1J2; J1/2; JP1/2; JP) and TCR- (Vd2D3; Vd1J1) gene rearrangements were performed according to Kiyoi et al,13 Landman-Parker et al,14 Davi et al,15 Delabesse et al,16 and Cave et al,17 respectively.     Results and discussion Top Abstract Introduction Study design Results and discussion References Clinical and biologic characteristics and outcome Clinical and hematologic findings are summarized in Table 2. They confirmed the association between M0 AML and older age, high WBC counts, CD7 expression, and high incidence of cytogenetic abnormalities.18-21 Median age of the 59 patients was 62 years. No patient was younger than 15 years, confirming the very low incidence of M0 AML in children. The morphology of blast cells was that of small to medium-sized blasts with high nucleocytoplasmic ratio and agranular basophilic cytoplasm and less often that of monocytoid-shaped blast, as previously reported.22 Morphologic and cytochemical data were not sufficient, and immunophenotypical studies were required in all cases for accurate diagnosis of M0 AML.                                View this table: [in this window] [in a new window]   Table 2. Pretreatment characteristics of M0 AML patients according to AML1 gene mutations Abnormal karyotype was found in 24 of 40 available cases and was complex ( 3 abnormalities) in 54% of them (Table 1). Aberrations involved preferentially chromosome 5, 7, 3, and 11. This high incidence of complex karyotypes with unbalanced changes such as 5/del(5q), 7, del(7q), and 3q abnormalities is usual in AML, occurring in elderly patients, and could partially explain the poor prognosis observed in our cohort. Abnormalities of chromosome 13 were found in only 2 cases, contrasting with a previous report that linked those abnormalities to M0 AML.20,22 Molecular and immunophenotypic findings are summarized in Table 1 and Figure 1. FLT3 duplication was found in 13 patients (22%) as compared with 16% of M0 AML in the recent series of Thiede et al.23 IgH or TCR gene rearrangement was found in 9 (15%) and 5 (8%), respectively, of the patients and were not correlated to lymphoid marker expression. One patient had simultaneous IgH and TCR rearrangements. View larger version (27K): [in this window] [in a new window]   Figure 1. Antigenic expression profile. The percentage of patients positive for the expression for each antigen for the whole series is compared with that of patients with AML1 gene mutation and without AML1 gene mutation. Gray bars indicate whole series of patients; black bars, patients with AML1 mutations; and white bars, patients without AML1 mutations. Three patients, aged 35, 47, and 64 years, died before onset of treatment. Nineteen patients received moderate single-agent chemotherapy or supportive care only, because of older age and/or poor clinical condition (18 of them were older than 70 years). Intensive chemotherapy was administered to the 37 remaining patients, of whom 23 (62%) achieved CR. Median CR duration was 12 months. Median survival of intensively treated patients was 10 months and 20 months in patients who achieved CR. Median survival of the whole cohort was 1 month (Figure 2A). Those results confirmed the poor prognosis of M0 AML, because of (besides frequent chromosomal rearrangements) the older age of many patients, who could not receive intensive chemotherapy.2,19,24 View larger version (5K): [in this window] [in a new window]   Figure 2. Survival of patients. (A) Kaplan-Meier overall survival of the whole series of patients. (B) Kaplan-Meier survival of patients intensively treated. (C) Kaplan-Meier survival according to FLT3 duplication in patients intensively treated: patient without FLT3 duplication, patients with FLT3 duplication, (P = .05 between the 2 groups). The poor prognosis of FLT3 duplication in other AMLs as a whole is now well documented.25 Here, in patients with M0 AML treated intensively, FLT3 duplication was the only prognostic factor with a median survival of 9 months in patients with FLT3 duplication versus 16 months in patients without FLT3 duplication (P = .05) (Figure 2C). AML1 mutation in the M0 AML population AML1 mutation was found in 16 patients (27%) (Table 2), an incidence similar to that observed in previous reports.3-6 All mutations involved the RUNT domain, were missense (n = 7) or stop codon mutation (n = 15), and were biallelic (except one case), therefore probably inactivating the AML1 protein. Those characteristics are similar to our preliminary results and show the strong correlation between lack of AML1 function and M0 AML subtype.26 In our M0 AML series, no differences were found between patients with or without AML1 mutations for age, sex, platelet count, hemoglobin value, myelodysplastic features, response to chemotherapy, and survival (Table 2). However, patients with AML1 mutation showed significantly higher leukocyte counts and higher marrow blast percentage, suggesting that AML1 mutations are associated with greater cell proliferation, lower incidence of CD33, and higher incidence of HLA-DR expression and higher frequency of IgH or TCR gene rearrangement. There was also a trend for lower incidence of chromosomal abnormalities and complex chromosomal abnormalities in our M0 AML cases with AML1 mutation. The higher incidence of IgH/TCR gene rearrangement in mutated cases could be related to AML1 loss of function. Indeed, AML1 has been reported to act as a transcriptional repressor by recruitment of transducinlike enhancer of split (TLE)/Groucho proteins.27 One of the target genes of this repression is TCR enhancer.28,29 AML1-mutated blast cells did not show expression of lymphoid markers, indicating absence of lymphoid differentiation, which could be linked to abnormal variable diversity joining (VDJ) recombination in myeloid-committed cells.30 However, we cannot exclude that AML1 mutation occurred only in very immature cells not committed to lymphoid or myeloid differentiation, in which TCR or immunoglobulin gene recombination would be a normal event.     Footnotes Submitted May 22, 2002; accepted September 6, 2002. Prepublished online as Blood First Edition Paper, October 10, 2002; DOI 10.1182/blood-2002-05-1474. Supported by the Centre Hospitalier Universitaire of Lille (PHRC 1997), The Ligue Nationale contre le cancer (Comité du Nord et de l'Aisne), and the Fondation de France (Comité Leucémie). P.F. and C.P. have equally contributed as last authors to this work. The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734. Reprints: Claude Preudhomme, Unité INSERM 524 and Laboratoire d'Hématologie A, 1 place de Verdun, Hôpital Calmette, 59037 Lille, France; e-mail: cpreudhomme{at}chru-lille.fr.     References Top Abstract Introduction Study design Results and discussion References 1. Lee EJ, Pollak A, Leavitt RD, Testa JR, Schiffer CA. Minimally differentiated acute nonlymphocytic leukemia: a distinct entity. Blood. 1987;70:1400-1406[Abstract]. 2. Amadori S, Venditti A, Del Poeta G, et al. Minimally differentiated acute myeloid leukemia (AML-M0): a distinct clinico-biologic entity with poor prognosis. Ann Hematol. 1996;72:208-215[CrossRef][Medline] [Order article via Infotrieve]. 3. Preudhomme C, Warot-Loze D, Roumier C, et al. High incidence of biallelic point mutations in the Runt domain of the AML1/PEBP2 alpha B gene in Mo acute myeloid leukemia and in myeloid malignancies with acquired trisomy 21. Blood. 2000;96:2862-2869[Abstract/Free Full Text]. 4. Osato M, Asou N, Abdalla E, et al. Biallelic and heterozygous point mutations in the runt domain of the AML1/PEBP2alphaB gene associated with myeloblastic leukemias. Blood. 1999;93:1817-1824[Abstract/Free Full Text]. 5. Langabeer SE, Gale RE, Rollinson SJ, Morgan GJ, Linch DC. Mutations of the AML1 gene in acute myeloid leukaemia of FAB types M0 and M7. Genes Chromosomes Cancer. 2002;34:24-32[CrossRef][Medline] [Order article via Infotrieve]. 6. Yeoh A, Williams K, Behm F, et al. Somatic mutations of the AML1 gene are frequent in acute myeloid leukemia with FAB M0 morphology (abstract). Blood. 2000;96:389. 7. Harousseau JL, Pignon B, Witz F, et al. Treatment of acute myeloblastic leukemia in adults: the GOELAM experience. Hematol Cell Ther. 1996;38:381-391[Medline] [Order article via Infotrieve]. 8. Zittoun R. The EORTC trials for acute myelogenous leukemia: EORTC Leukemia Cooperative Group: European Organisation of Research and Treatment of Cancer. Hematol Cell Ther. 1996;38:247-252[Medline] [Order article via Infotrieve]. 9. Reiffers J, Stoppa AM, Attal M, et al. Allogeneic vs autologous stem cell transplantation vs chemotherapy in patients with acute myeloid leukemia in first remission: the BGMT 87 study. Leukemia. 1996;10:1874-1882[Medline] [Order article via Infotrieve]. 10. Castaigne S, Archimbaud E, Fenaux P, et al. Place de la double induction dans le traitement des leucemies aigues myeloblastiques de l'adulte: resultats intermediaires du protocole LAM 90. Nouv Rev Fr Hematol. 1994;36(suppl 2):S139-S140[Medline] [Order article via Infotrieve]. 11. Bene MC, Castoldi G, Knapp W, et al. Proposals for the immunological classification of acute leukemias: European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia. 1995;9:1783-1786[Medline] [Order article via Infotrieve]. 12. Mitelman F, ed. International System for Cytogenetic Nomenclature. Guidelines for Cancer Cytogenetics, Supplement to an International System for Human Cytogenetic Nomenclature. Basel, Switzerland: Karger; 1995. 13. Kiyoi H, Naoe T, Nakano Y, et al. Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood. 1999;93:3074-3080[Abstract/Free Full Text]. 14. Landman-Parker J, Aubin J, Delabesse E, et al. Simplified strategies for minimal residual disease detection in B-cell precursor acute lymphoblastic leukaemia. Br J Haematol. 1996;95:281-290[Medline] [Order article via Infotrieve]. 15. Davi F, Faili A, Gritti C, et al. Early onset of immunoglobulin heavy chain gene rearrangements in normal human bone marrow CD34+ cells. Blood. 1997;90:4014-4021[Abstract/Free Full Text]. 16. Delabesse E, Burtin ML, Millien C, et al. Rapid, multifluorescent TCRG Vgamma and Jgamma typing: application to T cell acute lymphoblastic leukemia and to the detection of minor clonal populations. Leukemia. 2000;14:1143-1152[CrossRef][Medline] [Order article via Infotrieve]. 17. Cave H, Guidal C, Rohrlich P, et al. Prospective monitoring and quantitation of residual blasts in childhood acute lymphoblastic leukemia by polymerase chain reaction study of delta and gamma T-cell receptor genes. Blood. 1994;83:1892-1902[Abstract/Free Full Text]. 18. Venditti A, Del Poeta G, Buccisano F, et al. Minimally differentiated acute myeloid leukemia (AML-M0): comparison of 25 cases with other French-American-British subtypes. Blood. 1997;89:621-629[Abstract/Free Full Text]. 19. Venditti A, Del Poeta G, Stasi R, et al. Biological profile of 23 cases of minimally differentiated acute myeloid leukemia (AML-M0) and its clinical implications. Blood. 1996;87:418-420[Free Full Text]. 20. Cuneo A, Ferrant A, Michaux JL, et al. Cytogenetic profile of minimally differentiated (FAB M0) acute myeloid leukemia: correlation with clinicobiologic findings. Blood. 1995;85:3688-3694[Abstract/Free Full Text]. 21. Tien HF, Wang CH. CD7 positive hematopoietic progenitors and acute myeloid leukemia and other minimally differentiated leukemia. Leuk Lymphoma. 1998;31:93-98[Medline] [Order article via Infotrieve]. 22. Venditti A, Del Poeta G, Stasi R, et al. Minimally differentiated acute myeloid leukaemia (AML-M0): cytochemical, immunophenotypic and cytogenetic analysis of 19 cases. Br J Haematol. 1994;88:784-793[Medline] [Order article via Infotrieve]. 23. Thiede C, Steudel C, Mohr B, et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood. 2002;99:4326-4335[Abstract/Free Full Text]. 24. Bene MC, Bernier M, Casasnovas RO, et al. Acute myeloid leukaemia M0: haematological, immunophenotypic and cytogenetic characteristics and their prognostic significance: an analysis in 241 patients. Br J Haematol. 2001;113:737-745[CrossRef][Medline] [Order article via Infotrieve]. 25. Kottaridis PD, Gale RE, Frew ME, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001;98:1752-1759[Abstract/Free Full Text]. 26. Roumier C, Fenaux P, Lafage M, Imbert M, Eclache V, Preudhomme C. New mechanisms of AML1 gene alteration in hematological malignancies. Leukemia. In press. 27. Imai Y, Kurokawa M, Tanaka K, et al. TLE, the human homolog of groucho, interacts with AML1 and acts as a repressor of AML1-induced transactivation. Biochem Biophys Res Commun. 1998;252:582-589[CrossRef][Medline] [Order article via Infotrieve]. 28. Levanon D, Goldstein RE, Bernstein Y, et al. Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors. Proc Natl Acad Sci U S A. 1998;95:11590-11595[Abstract/Free Full Text]. 29. Lauzurica P, Zhong XP, Krangel MS, Roberts JL. Regulation of T cell receptor delta gene rearrangement by CBF/PEBP2. J Exp Med. 1997;185:1193-1201[Abstract/Free Full Text]. 30. Langerak AW, Wolvers-Tettero IL, van Gastel-Mol EJ, Oud ME, van Dongen JJ. Basic helix-loop-helix proteins E2A and HEB induce immature T-cell receptor rearrangements in nonlymphoid cells. Blood. 2001;98:2456-2465[Abstract/Free Full Text]. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Roudaia, M. D. Cheney, E. Manuylova, W. Chen, M. Morrow, S. Park, C.-T. Lee, P. Kaur, O. Williams, J. H. Bushweller, et al. CBF{beta} is critical for AML1-ETO and TEL-AML1 activity Blood, March 26, 2009; 113(13): 3070 - 3079. [Abstract] [Full Text] [PDF] L. Terriou, R. Ben Abdelali, C. Roumier, L. Lhermitte, J. de Vos, P. Cornillet, O. Nibourel, K. Beldjord, H. Dombret, G. Leverger, et al. C/EBPA methylation is common in T-ALL but not in M0 AML Blood, February 19, 2009; 113(8): 1864 - 1866. [Full Text] [PDF] F. P.G. Silva, A. Lind, G. Brouwer-Mandema, P. J.M. Valk, and M. Giphart-Gassler Trisomy 13 correlates with RUNX1 mutation and increased FLT3 expression in AML-M0 patients Haematologica, August 1, 2007; 92(8): 1123 - 1126. [Abstract] [Full Text] [PDF] D. Barbaric, T. A. Alonzo, R. B. Gerbing, S. Meshinchi, N. A. Heerema, D. R. Barnard, B. J. Lange, W. G. Woods, R. J. Arceci, and F. O. Smith Minimally differentiated acute myeloid leukemia (FAB AML-M0) is associated with an adverse outcome in children: a report from the Children's Oncology Group, studies CCG-2891 and CCG-2961 Blood, March 15, 2007; 109(6): 2314 - 2321. [Abstract] [Full Text] [PDF] U. Bacher, T. Haferlach, C. Schoch, W. Kern, and S. Schnittger Implications of NRAS mutations in AML: a study of 2502 patients Blood, May 15, 2006; 107(10): 3847 - 3853. [Abstract] [Full Text] [PDF] E. J. Jabbour, E. Estey, and H. M. Kantarjian Adult Acute Myeloid Leukemia Mayo Clin. Proc., February 1, 2006; 81(2): 247 - 260. [Abstract] [Full Text] [PDF] S. Schnittger, C. Schoch, W. Kern, C. Mecucci, C. Tschulik, M. F. Martelli, T. Haferlach, W. Hiddemann, and B. Falini Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype Blood, December 1, 2005; 106(12): 3733 - 3739. [Abstract] [Full Text] [PDF] J. D. Growney, H. Shigematsu, Z. Li, B. H. Lee, J. Adelsperger, R. Rowan, D. P. Curley, J. L. Kutok, K. Akashi, I. R. Williams, et al. Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype Blood, July 15, 2005; 106(2): 494 - 504. [Abstract] [Full Text] [PDF] This Article Abstract Full Text (PDF) All Versions of this Article: 2002-05-1474v1 101/4/1277    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Roumier, C. Articles by Preudhomme, C. Search for Related Content PubMed PubMed Citation Articles by Roumier, C. Articles by Preudhomme, C. Related Collections Neoplasia Brief Reports Clinical Trials and Observations Social Bookmarking                   What's this?

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020