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Blood, 1 February 2006, Vol. 107, No. 3, pp. 1242-1243. This Article Full Text (PDF) 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 Fröhling, S. Articles by Döhner, K. Search for Related Content PubMed PubMed Citation Articles by Fröhling, S. Articles by Döhner, K. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents CORRESPONDENCE To the editor: Rare occurrence of the JAK2 V617F mutation in AML subtypes M5, M6, and M7 It has recently been discovered that a single-site, clonal, gain-of-function mutation of the tyrosine kinase JAK2 (JAK2 V617F) is present in myeloid cells from the majority of patients with chronic myeloproliferative disorders (MPDs).1,2 In addition, JAK2 V617F can be detected in some patients with atypical chronic myeloid leukemia, chronic myelomonocytic leukemia (CMML), chronic neutrophilic leukemia, idiopathic hypereosinophilic syndrome, systemic mastocytosis, or myelodysplastic syndrome.3-6 Analysis of patients with acute myeloid leukemia (AML) has shown that JAK2 V617F is present in a significant proportion of patients with secondary AML following a preceding MPD.4,5 In contrast, the prevalence of JAK2 V617F in de novo AML has been reported to be very low3-5; however, data on the frequency of JAK2 V617F in specific subtypes of de novo AML are limited. The occurrence of JAK2 V617F in patients with CMML4-6; our previous observation that the HEL cell line, which was established from the peripheral blood of a patient with erythroleukemia (AML M6 as defined by the French-American-British classification),7 carries a homozygous JAK2 V617F mutation (GenBank accession no. AY973034 [GenBank] )8; and data showing that the JAK2/STAT5 signal transduction pathway is constitutively activated in megakaryocytic leukemic cell lines9 prompted us to analyze 85 patients with AML M5, 53 patients with AML M6, and 14 patients with AML M7 for the presence of JAK2 V617F. One hundred fifty of the 152 patients were treated according to protocols of the German-Austrian AML Study Group; the remaining 2 patients were treated outside a clinical trial. In addition, we studied 7 patients with secondary AML following a preceding MPD who had been treated at the University Hospital of Ulm. Mutational analysis of JAK2 exon 12 was performed as previously described.8 A heterozygous JAK2 V617F mutation was identified in 0 of 85 patients with AML M5, 1 of 53 patients with AML M6, and 0 of 14 patients with AML M7. These findings extend those of Jelinek et al,4 who detected JAK2 V617F in 0 of 20 cases with AML M0 through M5, 0 of 8 cases with AML M6, and 2 of 11 cases with AML M7. Of the 7 patients with secondary AML following a preceding MPD, 5 had JAK2 V617F: 3 cases with antecedent polycythemia vera, one case with pre-existing essential thrombocythemia, and one case with AML following idiopathic myelofibrosis. This observation is in accordance with 2 recent reports showing that the JAK2 V617F allele is common in patients who transform to AML from a pre-existing MPD.4,5 Our results indicate that the JAK2 V617F mutation is not a common event in the pathogenesis of AML M5, M6, and M7. Stefan Fröhling, Daniel B. Lipka, Sabine Kayser, Claudia Scholl, Richard F. Schlenk, Hartmut Döhner, D. Gary Gilliland, Ross L. Levine, and Konstanze Döhner Correspondence: Stefan Fröhling, Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, 1 Blackfan Circle, Boston, MA 02115; e-mail: sfrohling{at}rics.bwh.harvard.edu; or Ross L. Levine, Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, 1 Blackfan Circle, Boston, MA 02115; e-mail: rllevine{at}partners.org. Supported in part by National Institutes of Health grants, the Howard Hughes Medical Institute, the Leukemia and Lymphoma Society, and the Doris Duke Charitable Foundation (D.G.G.). S.F. is supported by grant FR 2113/1-1 from the Deutsche Forschungsgemeinschaft. C.S. is supported by grant SCHO 1215/1-1 from the Deutsche Forschungsgemeinschaft. S.F. and D.B.L. contributed equally to this work. References Goldman JM. A unifying mutation in chronic myeloproliferative disorders. N Engl J Med. 2005;352: 1744-1746.[Free Full Text] Kaushansky K. On the molecular origins of the chronic myeloproliferative disorders: it all makes sense. Blood. 2005;105: 4187-4190.[Free Full Text] Jones AV, Kreil S, Zoi K, et al. Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Prepublished on May 26, 2005, as DOI 10/1182/blood-2005-03-1320. (Now available as Blood. 2005;106: 2162-2168).[CrossRef] Jelinek J, Oki Y, Gharibyan V, et al. JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia-chromosome negative CML and megakaryocytic leukemia. Blood. Prepublished online on July 21, 2005, as DOI 10.1182/blood-2005-05-1800. (Now available as Blood. 2005;106: 3370-3373).[Abstract/Free Full Text] Levine RL, Loriaux M, Huntly BJ, et al. The JAK2 V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia. Blood. Prepublished online on August 4, 2005, as DOI 10.1182/blood-2005-05-1898. (Now available as Blood. 2005;106: 3377-3379).[Abstract/Free Full Text] Steensma DP, Dewald GW, Lasho TL, et al. The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both "atypical" myeloproliferative disorders and myelodysplastic syndromes. Blood. 2005;106: 1207-1209.[Abstract/Free Full Text] Martin P, Papayannopoulou T. HEL cells: a new human erythroleukemia cell line with spontaneous and induced globin expression. Science. 1982;216: 1233-1235.[Abstract/Free Full Text] Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7: 387-397.[CrossRef][Medline] [Order article via Infotrieve] Liu RY, Fan C, Garcia R, Jove R, Zuckerman KS. Constitutive activation of the JAK2/STAT5 signal transduction pathway correlates with growth factor independence of megakaryocytic leukemic cell lines. Blood. 1999;93: 2369-2379.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: On the molecular origins of the chronic myeloproliferative disorders: it all makes sense Kenneth Kaushansky Blood 2005 105: 4187-4190. [Full Text] [PDF] The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both "atypical" myeloproliferative disorders and myelodysplastic syndromes David P. Steensma, Gordon W. Dewald, Terra L. Lasho, Heather L. Powell, Rebecca F. McClure, Ross L. Levine, D. Gary Gilliland, and Ayalew Tefferi Blood 2005 106: 1207-1209. [Abstract] [Full Text] [PDF] Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders Amy V. Jones, Sebastian Kreil, Katerina Zoi, Katherine Waghorn, Claire Curtis, Lingyan Zhang, Joannah Score, Rachel Seear, Andrew J. Chase, Francis H. Grand, Helen White, Christine Zoi, Dimitris Loukopoulos, Evangelos Terpos, Elisavet-Christine Vervessou, Beate Schultheis, Michael Emig, Thomas Ernst, Eva Lengfelder, Rüdiger Hehlmann, Andreas Hochhaus, David Oscier, Richard T. Silver, Andreas Reiter, and Nicholas C. P. Cross Blood 2005 106: 2162-2168. [Abstract] [Full Text] [PDF] JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome–negative CML, and megakaryocytic leukemia Jaroslav Jelinek, Yasuhiro Oki, Vazganush Gharibyan, Carlos Bueso-Ramos, Josef T. Prchal, Srdan Verstovsek, Miloslav Beran, Elihu Estey, Hagop M. Kantarjian, and Jean-Pierre J. Issa Blood 2005 106: 3370-3373. [Abstract] [Full Text] [PDF] The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia Ross L. Levine, Marc Loriaux, Brian J. P. Huntly, Mignon L. Loh, Miroslav Beran, Eric Stoffregen, Roland Berger, Jennifer J. Clark, Stephanie G. Willis, Kim T. Nguyen, Nikki J. Flores, Elihu Estey, Norbert Gattermann, Scott Armstrong, A. Thomas Look, James D. Griffin, Olivier A. Bernard, Michael C. Heinrich, D. Gary Gilliland, Brian Druker, and Michael W. N. Deininger Blood 2005 106: 3377-3379. [Abstract] [Full Text] [PDF] This article has been cited by other articles: J. W. Tyner, D. K. Walters, S. G. Willis, M. Luttropp, J. Oost, M. Loriaux, H. Erickson, A. S. Corbin, T. O'Hare, M. C. Heinrich, et al. RNAi screening of the tyrosine kinome identifies therapeutic targets in acute myeloid leukemia Blood, February 15, 2008; 111(4): 2238 - 2245. [Abstract] [Full Text] [PDF] A. Theocharides, M. Boissinot, F. Girodon, R. Garand, S.-S. Teo, E. Lippert, P. Talmant, A. Tichelli, S. Hermouet, and R. C. Skoda Leukemic blasts in transformed JAK2-V617F-positive myeloproliferative disorders are frequently negative for the JAK2-V617F mutation. Blood, July 1, 2007; 110(1): 375 - 379. [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] T. Illmer, M. Schaich, G. Ehninger, C. Thiede, and on behalf of the DSIL2003 AML study group Tyrosine kinase mutations of JAK2 are rare events in AML but influence prognosis of patients with CBF-leukemias Haematologica, January 1, 2007; 92(1): 137 - 138. [Abstract] [Full Text] [PDF] P. J. Campbell and A. R. Green The Myeloproliferative Disorders N. Engl. J. Med., December 7, 2006; 355(23): 2452 - 2466. [Full Text] [PDF] H. Szpurka, R. Tiu, G. Murugesan, S. Aboudola, E. D. Hsi, K. S. Theil, M. A. Sekeres, and J. P. Maciejewski Refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T), another myeloproliferative condition characterized by JAK2 V617F mutation Blood, October 1, 2006; 108(7): 2173 - 2181. [Abstract] [Full Text] [PDF] D. P. Steensma JAK2 V617F in Myeloid Disorders: Molecular Diagnostic Techniques and Their Clinical Utility: A Paper from the 2005 William Beaumont Hospital Symposium on Molecular Pathology J. Mol. Diagn., September 1, 2006; 8(4): 397 - 411. 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