The JAK2-V617F mutation is frequently present at diagnosis in patients with essential thrombocythemia and polycythemia vera.

We determined the allelic frequency of the JAK2-V617F mutation in DNA and assessed the expression levels of the mutant and wild-type JAK2 mRNA in granulocytes from 60 patients with essential thrombocythemia (ET) and 62 patients with polycythemia vera (PV) at the time of diagnosis. Using allele-specific quantitative polymerase chain reaction (qPCR), we detected JAK2-V617F in 75% of ET and 97% of PV at diagnosis. The total JAK2 mRNA levels were elevated in ET, PV, and secondary and idiopathic erythrocytosis, suggesting that hyperactive hematopoiesis alters JAK2 expression. The expression levels of JAK2-V617F mRNA were variable but strongly correlated with the allelic ratio of JAK2-V617F determined in DNA. Thus, differences in JAK2-V617F expression, markedly lower in ET than in PV, reflected different percentages of granulocytes carrying the mutation. Moreover, allelic ratios higher than 50% JAK2-V617F, indicating the presence of granulocytes homozygous for JAK2-V617F, were found in 70% of PV at diagnosis but never in ET.

[1]  Sandra A. Moore,et al.  Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. , 2005, Cancer cell.

[2]  F. Watzinger,et al.  Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using ‘real-time’ quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR) – a Europe against cancer program , 2003, Leukemia.

[3]  N. Harris,et al.  The World Health Organization (WHO) classification of the myeloid neoplasms. , 2002, Blood.

[4]  E. Juvonen,et al.  Proposal for Revised Diagnostic Criteria of Essential Thrombocythemia and Polycythemia Vera by the Thrombocythemia Vera Study Group , 1997, Seminars in thrombosis and hemostasis.

[5]  Mario Cazzola,et al.  A gain-of-function mutation of JAK2 in myeloproliferative disorders. , 2005, The New England journal of medicine.

[6]  F. Girodon,et al.  Standardization and comparison of endogenous erythroid colony assays performed with bone marrow or blood progenitors for the diagnosis of polycythemia vera. , 2004, The hematology journal : the official journal of the European Haematology Association.

[7]  F. Girodon,et al.  Comparison of four serum-free, cytokine-free media for analysis of endogenous erythroid colony growth in polycythemia vera and essential thrombocythemia. , 2001, The hematology journal : the official journal of the European Haematology Association.

[8]  R. Levine,et al.  X-inactivation-based clonality analysis and quantitative JAK2V617F assessment reveal a strong association between clonality and JAK2V617F in PV but not ET/MMM, and identifies a subset of JAK2V617F-negative ET and MMM patients with clonal hematopoiesis. , 2005, Blood.

[9]  H. Heimpel,et al.  Quantification of PRV-1 mRNA distinguishes polycythemia vera from secondary erythrocytosis. , 2003, Blood.

[10]  E. Lippert,et al.  A standardized endogenous megakaryocytic erythroid colony assay for the diagnosis of essential thrombocythemia. , 2004, Haematologica.

[11]  M. Cazzola,et al.  Gain of function, loss of control - a molecular basis for chronic myeloproliferative disorders. , 2005, Haematologica.

[12]  M. Cazzola,et al.  Altered gene expression in myeloproliferative disorders correlates with activation of signaling by the V 617 F mutation of Jak 2 , 2005 .

[13]  H. Heimpel,et al.  The Jak2V617F mutation, PRV-1 overexpression, and EEC formation define a similar cohort of MPD patients. , 2005, Blood.

[14]  D. Gilliland,et al.  Concomitant neutrophil JAK2V617F mutation screening and PRV‐1 expression analysis in myeloproliferative disorders and secondary polycythaemia , 2005, British journal of haematology.

[15]  F. Girodon,et al.  Diagnostic value of serum erythropoietin level in patients with absolute erythrocytosis. , 2004, Haematologica.

[16]  P. Campbell,et al.  Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders , 2005, The Lancet.

[17]  M. Cazzola,et al.  Altered gene expression in myeloproliferative disorders correlates with activation of signaling by the V617F mutation of Jak2. , 2005, Blood.

[18]  Stefan N. Constantinescu,et al.  A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera , 2005, Nature.

[19]  P. Campbell,et al.  Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study , 2005, The Lancet.