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JAK2 V617F mutation in classic chronic myeloproliferative diseases: a report on a series of 349 patients

Leukemia volume 20, pages 534–535 (2006)Cite this article

Several groups have recently reported the presence of a unique gain-of-function JAK2 point mutation (V617F) in the majority of cases of classic cMPD as well as in a minority of atypical MPDs and in occasional cases of AML. To date, this mutation has not been reported in normal controls, lymphoid disorders or in patients with secondary erythrocytosis.1, 2, 3, 4, 5, 6, 7, 8, 9, 10

In this study, we have analyzed bone marrow or peripheral blood samples from 349 patients (PV, n=84; ET, n=243; IMF, n=22) referred to our diagnostic service for cytogenetic analysis and/or exclusion of the BCR-ABL fusion from several hospitals in the north of Spain between 1996 and 2005. Our study group thus includes the largest series of ET cases reported to date for JAK2 analysis. DNA was extracted and tested for V617F by a sensitive amplification refractory mutation system as described previously.6 Results were obtained from all samples and V617F was detected in 80, 62 and 68% of cases of PV, ET and IMF, respectively (Table 1). These frequencies are comparable to other studies for PV and IMF, but somewhat higher than expected for ET, for which 23–57% of cases have been reported as V617F positive. Part of the reason for this is probably attributable to technical differences in the sensitivity of the V617F detection. Most other studies used sequencing, which can underestimate the proportion of positive patients,2, 6 whereas allele-specific PCR assay is capable of detecting a mutation present in 1–2% of cells.6

Table 1 JAK2 V617F mutation frequencies (separated by gender)
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References

  1. James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005; 434: 1144–1148.

    Article  CAS  Google Scholar 

  2. Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S et al. Cancer Genome Project. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005; 365: 1054–1061.

    Article  CAS  Google Scholar 

  3. Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ 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.

    Article  CAS  Google Scholar 

  4. Zhao R, Xing S, Li Z, Fu X, Li Q, Krantz SB et al. Identification of an acquired JAK2 mutation in polycythemia vera. J Biol Chem 2005; 280: 22788–22792.

    Article  CAS  Google Scholar 

  5. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005; 352: 1779–1790.

    Article  CAS  Google Scholar 

  6. Jones AV, Kreil S, Zoi K, Waghorn K, Curtis C, Zhang L et al. Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood 2005; 106: 2162–2168.

    Article  CAS  Google Scholar 

  7. Steensma DP, Dewald GW, Lasho TL, Powell HL, McClure RF, Levine RL 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.

    Article  CAS  Google Scholar 

  8. Jelinek J, Oki Y, Gharibyan V, Bueso-Ramos C, Prchal JT, Verstovsek S 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 2005; 106: 3370–3373.

    Article  CAS  Google Scholar 

  9. Goerttler PS, Steimle C, Marz E, Johansson PL, Andreasson B, Griesshammer M et al. The Jak2V617F mutation, PRV-1 overexpression and EEC formation define a similar cohort of MPD patients. Blood 2005; 106: 2862–2864.

    Article  CAS  Google Scholar 

  10. Wolanskyj AP, Lasho TL, Schwager SM, McClure RF, Wadleigh M, Lee SJ et al. JAK2 mutation in essential thrombocythaemia: clinical associations and long-term prognostic relevance. Br J Haematol 2005; 131: 208–213.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Virginia Cebrián, Iñigo Landa and Beatriz Sánchez for technical assistance. This work was supported by Grant 05/2003 from the Department of Health of the Government of Navarra, Spain, and by Grant FIS 04/0037 from Instituto de Salud Carlos III.

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Authors and Affiliations

  1. Department of Genetics, School of Science, University of Navarra, Pamplona, Spain

    J L Vizmanos, C Ormazábal, M J Larráyoz & M J Calasanz

  2. Salisbury and Human Genetics Division, Wessex Regional Genetics Laboratory, University of Southampton, Southampton, UK

    N C P Cross

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Correspondence to J L Vizmanos.

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Vizmanos, J., Ormazábal, C., Larráyoz, M. et al. JAK2 V617F mutation in classic chronic myeloproliferative diseases: a report on a series of 349 patients. Leukemia 20, 534–535 (2006). https://doi.org/10.1038/sj.leu.2404086

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