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Clinical correlates of JAK2V617F presence or allele burden in myeloproliferative neoplasms: a critical reappraisal

Leukemia volume 22, pages 1299–1307 (2008)Cite this article

Abstract

JAK2 and MPL mutations are recurrent in myeloproliferative neoplasms (MPNs). A JAK2 mutation, primarily JAK2V617F, is almost invariably associated with polycythemia vera (PV). However, JAK2V617F also occurs in the majority of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF) as well as in a much smaller percentage of those with other MPNs. The mechanism(s) behind this one allele-multiple phenotypes phenomenon has not been fully elucidated. The issue is further confounded by the presence of marked variation in JAK2V617F allele burden among mutation-positive patients. In the current communication, we discuss potential mechanisms for phenotypic diversity among JAK2V617F-positive MPNs as well as review the current literature in regard to genotype–phenotype correlations (that is clinical correlates and prognostic significance) in the context of both the presence or absence of the mutation (ET and PMF) and its allele burden (PV, ET and PMF).

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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  PubMed  Google Scholar 

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

    Article  CAS  PubMed  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  PubMed  Google Scholar 

  4. 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  PubMed  Google Scholar 

  5. Scott LM, Tong W, Levine RL, Scott MA, Beer PA, Stratton MR et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 2007; 356: 459–468.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 2006; 3: e270.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Pardanani AD, Levine RL, Lasho T, Pikman Y, Mesa RA, Wadleigh M et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 2006; 108: 3472–3476.

    Article  CAS  PubMed  Google Scholar 

  8. Vannucchi AM, Antonioli E, Pancrazzi A, Guglielmelli P, Di Lollo S, Alterini R et al. The clinical phenotype of patients with essential thrombocythemia harboring MPL W515l/K mutation. Blood 2007; 110, (abstract 678).

  9. Williams DM, Kim AH, Rogers O, Spivak JL, Moliterno AR . Phenotypic variations and new mutations in JAK2 V617F-negative polycythemia vera, erythrocytosis, and idiopathic myelofibrosis. Exp Hematol 2007; 35: 1641–1646.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Beer PA, Campbell P, Erber WN, Scott LM, Bench AJ, Bareford D et al. Clinical significance of MPL mutation in essential thrombocythemia: analysis of the PT-1 cohort. Blood 2007; 110, (abstract 677).

  11. Ding J, Komatsu H, Wakita A, Kato-Uranishi M, Ito M, Satoh A et al. Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin. Blood 2004; 103: 4198–4200.

    Article  CAS  PubMed  Google Scholar 

  12. Dameshek W . Some speculations on the myeloproliferative syndromes. Blood 1951; 6: 372–375.

    CAS  PubMed  Google Scholar 

  13. Spivak JL . Diagnosis of the myeloproliferative disorders: resolving phenotypic mimicry. Semin Hematol 2003; 40: 1–5.

    Article  PubMed  Google Scholar 

  14. Levine RL, Pardanani A, Tefferi A, Gilliland DG . Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders. Nat Rev Cancer 2007; 7: 673–683.

    Article  CAS  PubMed  Google Scholar 

  15. Vainchenker W, Constantinescu SN . A Unique Activating Mutation in JAK2 (V617F) Is at the Origin of Polycythemia Vera and Allows a New Classification of Myeloproliferative Diseases. Hematology Am Soc Hematol Educ Program 2005, 195–200.

    Article  Google Scholar 

  16. Prchal JF, Axelrad AA . Letter: bone-marrow responses in polycythemia vera. N Engl J Med 1974; 290: 1382.

    CAS  PubMed  Google Scholar 

  17. Dupont S, Masse A, James C, Teyssandier I, Lecluse Y, Larbret F et al. The JAK2 V617F mutation triggers erythropoietin hypersensitivity and terminal erythroid amplification in primary cells from patients with polycythemia vera. Blood 2007; 110: 1013–1021.

    Article  CAS  PubMed  Google Scholar 

  18. Delhommeau F, Pisani DF, James C, Casadevall N, Constantinescu S, Vainchenker W . Oncogenic mechanisms in myeloproliferative disorders. Cell Mol Life Sci 2006; 63: 2939–2953.

    Article  CAS  PubMed  Google Scholar 

  19. Taksin AL, Couedic JP, Dusanter-Fourt I, Masse A, Giraudier S, Katz A et al. Autonomous megakaryocyte growth in essential thrombocythemia and idiopathic myelofibrosis is not related to a c-mpl mutation or to an autocrine stimulation by Mpl-L. Blood 1999; 93: 125–139.

    CAS  PubMed  Google Scholar 

  20. Parganas E, Wang D, Stravopodis D, Topham DJ, Marine JC, Teglund S et al. Jak2 is essential for signaling through a variety of cytokine receptors. Cell 1998; 93: 385–395.

    Article  CAS  PubMed  Google Scholar 

  21. Jamieson CH, Gotlib J, Durocher JA, Chao MP, Mariappan MR, Lay M et al. The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation. Proc Natl Acad Sci USA 2006; 103: 6224–6229.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bogani C, Guglielmelli P, Antonioli E, Pancrazzi A, Bosi A, Vannucchi AM . B-, T-, and NK-cell lineage involvement in JAK2V617F-positive patients with idiopathic myelofibrosis. Haematologica 2007; 92: 258–259.

    Article  PubMed  Google Scholar 

  23. Ishii T, Bruno E, Hoffman R, Xu M . Involvement of various hematopoietic-cell lineages by the JAK2V617F mutation in polycythemia vera. Blood 2006; 108: 3128–3134.

    Article  CAS  PubMed  Google Scholar 

  24. Pardanani A, Lasho TL, Finke C, Mesa RA, Hogan WJ, Ketterling RP et al. Extending JAK2V617F and MPLW515 mutation analysis to single hematopoietic colonies and B- and T-lymphocytes. Stem Cells 2007; 25: 2358–2362.

    Article  CAS  PubMed  Google Scholar 

  25. Lasho TL, Mesa R, Gilliland DG, Tefferi A . Mutation studies in CD3+, CD19+ and CD34+ cell fractions in myeloproliferative disorders with homozygous JAK2(V617F) in granulocytes. Br J Haematol 2005; 130: 797–799.

    Article  CAS  PubMed  Google Scholar 

  26. Lasho TL, Pardanani A, McClure RF, Mesa RA, Levine RL, Gilliland DG et al. Concurrent MPL515 and JAK2V617F mutations in myelofibrosis: chronology of clonal emergence and changes in mutant allele burden over time. Br J Haematol 2006; 135: 683–687.

    Article  CAS  PubMed  Google Scholar 

  27. Pardanani A, Lasho TL, Finke C, Markovic SN, Tefferi A . Demonstration of MPLW515K, but not JAK2V617F, in in vitro expanded CD4+ T lymphocytes. Leukemia 2007; 21: 2206–2207.

    Article  CAS  PubMed  Google Scholar 

  28. Delhommeau F, Dupont S, Tonetti C, Masse A, Godin I, Le Couedic JP et al. Evidence that the JAK2 G1849T (V617F) mutation occurs in a lymphomyeloid progenitor in polycythemia vera and idiopathic myelofibrosis. Blood 2007; 109: 71–77.

    Article  CAS  PubMed  Google Scholar 

  29. Scott LM, Scott MA, Campbell PJ, Green AR . Progenitors homozygous for the V617F mutation occur in most patients with polycythemia vera, but not essential thrombocythemia. Blood 2006; 108: 2435–2437.

    Article  CAS  PubMed  Google Scholar 

  30. Kralovics R, Teo SS, Buser AS, Brutsche M, Tiedt R, Tichelli A et al. Altered gene expression in myeloproliferative disorders correlates with activation of signaling by the V617F mutation of Jak2. Blood 2005; 106: 3374–3376.

    Article  CAS  PubMed  Google Scholar 

  31. Vannucchi AM, Guglielmelli P, Antonioli E, Mappa S, Pancrazzi A, Bogani C et al. Inconsistencies in the association between the JAK2(V617F) mutation and PRV-1 over-expression among the chronic myeloproliferative diseases. Br J Haematol 2006; 132: 652–654.

    Article  PubMed  Google Scholar 

  32. Vannucchi AM, Pancrazzi A, Bogani C, Antonioli E, Guglielmelli P . A quantitative assay for JAK2(V617F) mutation in myeloproliferative disorders by ARMS-PCR and capillary electrophoresis. Leukemia 2006; 20: 1055–1060.

    Article  CAS  PubMed  Google Scholar 

  33. 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  PubMed  Google Scholar 

  34. Passamonti F, Rumi E, Pietra D, Della Porta MG, Boveri E, Pascutto C et al. Relation between JAK2 (V617F) mutation status, granulocyte activation, and constitutive mobilization of CD34+ cells into peripheral blood in myeloproliferative disorders. Blood 2006; 107: 3676–3682.

    Article  CAS  PubMed  Google Scholar 

  35. Guglielmelli P, Zini R, Bogani C, Salati S, Pancrazzi A, Bianchi E et al. Molecular profiling of CD34+ cells in idiopathic myelofibrosis identifies a set of disease-associated genes and reveals the clinical significance of Wilms’ tumor gene 1 (WT1). Stem Cells 2007; 25: 165–173.

    CAS  PubMed  Google Scholar 

  36. Hookham MB, Elliott J, Suessmuth Y, Staerk J, Ward AC, Vainchenker W et al. The myeloproliferative disorder-associated JAK2 V617F mutant escapes negative regulation by suppressor of cytokine signaling 3. Blood 2007; 109: 4924–4929.

    Article  CAS  PubMed  Google Scholar 

  37. Wernig G, Mercher T, Okabe R, Levine RL, Lee BH, Gilliland DG . Expression of Jak2V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow transplant model. Blood 2006; 107: 4274–4281.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Lacout C, Pisani DF, Tulliez M, Gachelin FM, Vainchenker W, Villeval JL . JAK2V617F expression in murine hematopoietic cells leads to MPD mimicking human PV with secondary myelofibrosis. Blood 2006; 108: 1652–1660.

    CAS  PubMed  Google Scholar 

  39. Bumm TG, Elsea C, Corbin AS, Loriaux M, Sherbenou D, Wood L et al. Characterization of murine JAK2V617F-positive myeloproliferative disease. Cancer Res 2006; 66: 11156–11165.

    CAS  PubMed  Google Scholar 

  40. Zaleskas VM, Krause DS, Lazarides K, Patel N, Hu Y, Li S et al. Molecular pathogenesis and therapy of polycythemia induced in mice by JAK2 V617F. PLoS ONE 2006; 1: e18.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Shide K, Shimoda HK, Kumano T, Karube K, Kameda T, Takenaka K et al. Development of ET, primary myelofibrosis and PV in mice expressing JAK2 V617F. Leukemia 2008; 22: 87–95.

    Article  CAS  PubMed  Google Scholar 

  42. Tiedt R, Hao-Shen H, Sobas MA, Looser R, Dimhofer S, Schwaller J et al. Ratio of mutant JAK2-V617F to wild-type Jak2 determines the MPD phenotypes in transgenic mice. Blood 2008; 111: 3931–3940.

    Article  CAS  PubMed  Google Scholar 

  43. Campbell PJ, Green AR . The myeloproliferative disorders. N Engl J Med 2006; 355: 2452–2466.

    Article  CAS  PubMed  Google Scholar 

  44. Pardanani A, Fridley BL, Lasho TL, Gilliland DG, Tefferi A . Host genetic variation contributes to phenotypic diversity in myeloproliferative disorders. Blood 2008; 111: 2785–2789.

    Article  CAS  PubMed  Google Scholar 

  45. Antonioli E, Guglielmelli P, Pancrazzi A, Bogani C, Verrucci M, Ponziani V et al. Clinical implications of the JAK2 V617F mutation in essential thrombocythemia. Leukemia 2005; 19: 1847–1849.

    Article  CAS  PubMed  Google Scholar 

  46. Kralovics R, Teo SS, Li S, Theocharides A, Buser AS, Tichelli A et al. Acquisition of the V617F mutation of JAK2 is a late genetic event in a subset of patients with myeloproliferative disorders. Blood 2006; 108: 1377–1380.

    Article  CAS  PubMed  Google Scholar 

  47. Gale RE, Allen AJ, Nash MJ, Linch DC . Long-term serial analysis of X-chromosome inactivation patterns and JAK2 V617F mutant levels in patients with essential thrombocythemia show that minor mutant-positive clones can remain stable for many years. Blood 2007; 109: 1241–1243.

    Article  CAS  PubMed  Google Scholar 

  48. Gaikwad A, Nussenzveig R, Liu E, Gottshalk S, Chang K, Prchal JT . In vitro expansion of erythroid progenitors from polycythemia vera patients leads to decrease in JAK2 V617F allele. Exp Hematol 2007; 35: 587–595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Nussenzveig RH, Swierczek SI, Jelinek J, Gaikwad A, Liu E, Verstovsek S et al. Polycythemia vera is not initiated by JAK2V617F mutation. Exp Hematol 2007; 35: 32–38.

    Article  CAS  PubMed  Google Scholar 

  50. Theocharides A, Boissinot M, Girodon F, Garand R, Teo SS, Lippert E et al. Leukemic blasts in transformed JAK2-V617F-positive myeloproliferative disorders are frequently negative for the JAK2-V617F mutation. Blood 2007; 110: 375–379.

    Article  CAS  PubMed  Google Scholar 

  51. Skoda R . The genetic basis of myeloproliferative disorders. Hematology Am Soc Hematol Educ Program 2007; 2007: 1–10.

    Article  Google Scholar 

  52. Campbell PJ, Scott LM, Buck G, Wheatley K, East CL, Marsden JT et al. Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study. Lancet 2005; 366: 1945–1953.

    CAS  PubMed  Google Scholar 

  53. 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  PubMed  Google Scholar 

  54. Cheung B, Radia D, Pantelidis P, Yadegarfar G, Harrison C . The presence of the JAK2 V617F mutation is associated with a higher haemoglobin and increased risk of thrombosis in essential thrombocythaemia. Br J Haematol 2006; 132: 244–245.

    Article  CAS  PubMed  Google Scholar 

  55. Kittur J, Knudson RA, Lasho TL, Finke CM, Gangat N, Wolanskyj AP et al. Clinical correlates of JAK2V617F allele burden in essential thrombocythemia. Cancer 2007; 109: 2279–2284.

    Article  PubMed  Google Scholar 

  56. Pemmaraju N, Moliterno AR, Williams DM, Rogers O, Spivak JL . The quantitative JAK2 V617F neutrophil allele burden does not correlate with thrombotic risk in essential thrombocytosis. Leukemia 2007; 21: 2210–2212.

    Article  CAS  PubMed  Google Scholar 

  57. Finazzi G, Rambaldi A, Guerini V, Carobbo A, Barbui T . Risk of thrombosis in patients with essential thrombocythemia and polycythemia vera according to JAK2 V617F mutation status. Haematologica 2007; 92: 135–136.

    Article  PubMed  Google Scholar 

  58. Rudzki Z, Sacha T, Stoj A, Czekalska S, Wojcik M, Skotnicki AB et al. The gain-of-function JAK2 V617F mutation shifts the phenotype of essential thrombocythemia and chronic idiopathic myelofibrosis to more ‘erythremic’ and less ‘thrombocythemic’: a molecular, histologic, and clinical study. Int J Hematol 2007; 86: 130–136.

    Article  CAS  PubMed  Google Scholar 

  59. Heller PG, Lev PR, Salim JP, Kornblihtt LI, Goette NP, Chazarreta CD et al. JAK2V617F mutation in platelets from essential thrombocythemia patients: correlation with clinical features and analysis of STAT5 phosphorylation status. Eur J Haematol 2006; 77: 210–216.

    Article  CAS  PubMed  Google Scholar 

  60. Alvarez-Larran A, Cervantes F, Bellosillo B, Giralt M, Julia A, Hernandez-Boluda JC et al. Essential thrombocythemia in young individuals: frequency and risk factors for vascular events and evolution to myelofibrosis in 126 patients. Leukemia 2007; 21: 1218–1223.

    Article  CAS  PubMed  Google Scholar 

  61. Vannucchi AM, Antonioli E, Guglielmelli P, Rambaldi A, Barosi G, Marchioli R et al. Clinical profile of homozygous JAK2V617F mutation in patients with polycythemia vera or essential thrombocythemia. Blood 2007; 110: 840–846.

    Article  CAS  PubMed  Google Scholar 

  62. Antonioli E, Guglielmelli P, Poli G, Bogani C, Pancrazzi A, Longo G et al. Influence of JAK2V617F allele burden on phenotype in essential thrombocythemia. Haematologica 2008; 93: 41–48.

    Article  CAS  PubMed  Google Scholar 

  63. Campbell PJ, Griesshammer M, Dohner K, Dohner H, Kusec R, Hasselbalch HC et al. V617F mutation in JAK2 is associated with poorer survival in idiopathic myelofibrosis. Blood 2006; 107: 2098–2100.

    Article  CAS  PubMed  Google Scholar 

  64. Tefferi A, Lasho TL, Schwager SM, Steensma DP, Mesa RA, Li CY et al. The JAK2(V617F) tyrosine kinase mutation in myelofibrosis with myeloid metaplasia: lineage specificity and clinical correlates. Br J Haematol 2005; 131: 320–328.

    Article  CAS  PubMed  Google Scholar 

  65. Barosi G, Bergamaschi G, Marchetti M, Vannucchi AM, Guglielmelli P, Antonioli E et al. JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis. Blood 2007; 110: 4030–4036.

    Article  CAS  PubMed  Google Scholar 

  66. Tefferi A, Lasho TL, Huang J, Finke C, Hanson CA, Mesa RA et al. Low JAK2V617F allele burden in primary myelofibrosis, compared to either a higher allele burden or unmutated status, predicts inferior overall and leukemia-free survival. Leukemia 2008; 22: 756–761.

    Article  CAS  PubMed  Google Scholar 

  67. Finazzi G, Barbui T . Risk-adapted therapy in essential thrombocythemia and polycythemia vera. Blood Rev 2005; 19: 243–252.

    Article  PubMed  Google Scholar 

  68. Carobbio A, Finazzi G, Guerini V, Spinelli O, Delaini F, Marchioli R et al. Leukocytosis is a risk factor for thrombosis in essential thrombocythemia: interaction with treatment, standard risk factors, and Jak2 mutation status. Blood 2007; 109: 2310–2313.

    Article  CAS  PubMed  Google Scholar 

  69. Tefferi A, Lasho TL, Schwager SM, Strand JS, Elliott M, Mesa R et al. The clinical phenotype of wild-type, heterozygous, and homozygous JAK2V617F in polycythemia vera. Cancer 2006; 106: 631–635.

    Article  CAS  PubMed  Google Scholar 

  70. Larsen TS, Pallisgaard N, Moller MB, Hasselbalch HC . The JAK2 V617F allele burden in essential thrombocythemia, polycythemia vera and primary myelofibrosis - impact on disease phenotype. Eur J Haematol 2007; 79: 508–515.

    Article  CAS  PubMed  Google Scholar 

  71. Mesa RA, Powell H, Lasho T, DeWald GW, McClure R, Tefferi A . A longitudinal study of the JAK2(V617F) mutation in myelofibrosis with myeloid metaplasia: analysis at two time points. Haematologica 2006; 91: 415–416.

    CAS  PubMed  Google Scholar 

  72. Antonioli E, Guglielmelli P, Poli G, Bogani C, Pancrazzi A, Longo G et al. Influence of JAK2V617F allele burden on phenotype in essential thrombocythemia. Haematologica 2008; 93: 41–48.

    Article  CAS  PubMed  Google Scholar 

  73. Vannucchi AM, Antonioli E, Guglielmelli P, Longo G, Pancrazzi A, Ponziani V et al. Prospective identification of high-risk polycythemia vera patients based on JAK2(V617F) allele burden. Leukemia 2007; 21: 1952–1959.

    Article  CAS  PubMed  Google Scholar 

  74. Tefferi A, Strand JJ, Lasho TL, Knudson RA, Finke CM, Gangat N et al. Bone marrow JAK2V617F allele burden and clinical correlates in polycythemia vera. Leukemia 2007; 21: 2074–2075.

    Article  CAS  PubMed  Google Scholar 

  75. Silver RT, Vandris K, Wang LY, Christos PJ, DAdriano F, Jones AV et al. JAK2V617F mutational load in patients with polycythemia vera measured by peripheral blood DNA is associated with disease severity. Blood 2007; 110, (abstract 2530).

  76. Hermouet S, Dobo I, Lippert E, Boursier MC, Ergand L, Perrault-Hu F et al. Comparison of whole blood vs purified blood granulocytes for the detection and quantitation of JAK2(V617F). Leukemia 2007; 21: 1128–1130.

    Article  CAS  PubMed  Google Scholar 

  77. Steensma DP . 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 2006; 8: 397–411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Lippert E, Boissinot M, Kralovics R, Girodo-n F, Dobo I, Praloran V et al. The JAK2-V617F mutation is frequently present at diagnosis in patients with essential thrombocythemia and polycythemia vera. Blood 2006; 108: 1865–1867.

    Article  CAS  PubMed  Google Scholar 

  79. Larsen TS, Pallisgaard N, Moller MB, Hasselbalch HC . Quantitative assessment of the JAK2 V617F allele burden: equivalent levels in peripheral blood and bone marrow. Leukemia 2008; 22: 194–195.

    Article  CAS  PubMed  Google Scholar 

  80. Moliterno AR, Williams DM, Rogers O, Isaac MA, Spivak JL . Clonal dominance at the progenitor cell level defines clinical phenotype more accurately than the neutrophil allele burden in JAK2V617F-positive MPD patients. Blood 2007; 110, (abstract 679).

  81. Jones AV, Silver RT, Waghorn K, Curtis C, Kreil S, Zoi K et al. Minimal molecular response in polycythemia vera patients treated with imatinib or interferon alpha. Blood 2006; 107: 3339–3341.

    Article  CAS  PubMed  Google Scholar 

  82. Kiladjian JJ, Cassinat B, Turlure P, Cambier N, Roussel M, Bellucci S et al. High molecular response rate of polycythemia vera patients treated with pegylated interferon alpha-2a. Blood 2006; 108: 2037–2040.

    Article  CAS  PubMed  Google Scholar 

  83. Tefferi A, Lasho TL, Mesa RA, Pardanani A, Ketterling RP, Hanson CA . Lenalidomide therapy in del(5)(q31)-associated myelofibrosis: cytogenetic and JAK2V617F molecular remissions. Leukemia 2007; 21: 1827–1828.

    CAS  PubMed  Google Scholar 

  84. Helbig G, Stella-Holowiecka B, Majewski M, Lewandowska M, Holowiecki J . Interferon alpha induces a good molecular response in a patient with chronic eosinophilic leukemia (CEL) carrying the JAK2V617F point mutation. Haematologica 2007; 92: e118–e119.

    Article  CAS  PubMed  Google Scholar 

  85. Kroger N, Badbaran A, Holler E, Hahn J, Kobbe G, Bornhauser M et al. Monitoring of the JAK2-V617F mutation by highly sensitive quantitative real-time PCR after allogeneic stem cell transplantation in patients with myelofibrosis. Blood 2007; 109: 1316–1321.

    Article  PubMed  Google Scholar 

  86. Prchal JT . The amount of JAK2 617V>F matters. Blood 2007; 110: 796–797.

    Article  CAS  Google Scholar 

  87. Pardanani A . JAK2 inhibitor therapy in myeloproliferative disorders: rationale, preclinical studies and ongoing clinical trials. Leukemia 2008; 22: 23–30.

    Article  CAS  PubMed  Google Scholar 

  88. Landolfi R, Di Gennaro L, Barbui T, De Stefano V, Finazzi G, Marfisi R et al. Leukocytosis as a major thrombotic risk factor in patients with polycythemia vera. Blood 2007; 109: 2446–2452.

    Article  CAS  PubMed  Google Scholar 

  89. Tefferi A, Gangat N, Wolanskyj A . The interaction between leukocytosis and other risk factors for thrombosis in essential thrombocythemia. Blood 2007; 109: 4105.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study was supported by Associazione Italiana per la Ricerca sul Cancro, Milano, and projects from Ministero Italiano della Università e Ricerca (COFIN 2006067001_003) to AMV.

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Authors and Affiliations

  1. Dipartimento di Area Critica Medico-Chirurgica, UF di Ematologia, Università degli Studi, Azienda Ospedaliera-Universitaria Careggi, Firenze, Italy

    A M Vannucchi, E Antonioli & P Guglielmelli

  2. Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    A Pardanani & A Tefferi

  3. Istituto Toscano Tumori, Firenze, Italy

    A M Vannucchi, E Antonioli & P Guglielmelli

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  1. A M Vannucchi
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Correspondence to A M Vannucchi.

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Vannucchi, A., Antonioli, E., Guglielmelli, P. et al. Clinical correlates of JAK2V617F presence or allele burden in myeloproliferative neoplasms: a critical reappraisal. Leukemia 22, 1299–1307 (2008). https://doi.org/10.1038/leu.2008.113

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