A prospective study of 338 patients with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications

Passamonti, Francesco; Rumi, Elisa; Pietra, Daniela; Elena, Chiara; Boveri, Emanuela; Arcaini, Luca; Roncoroni, Elisa; Astori, Cesare; Merli, Michele; Boggi, Sabrina; Pascutto, Cristiana; Lazzarino, Mario; Cazzola, Mario

doi:10.1038/leu.2010.148

Cited by 334 publications

(313 citation statements)

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“…Risk factors for leukemic transformation in PV include advanced age, leukocytosis, and abnormal karyotype [50]. On the other hand, JAK2V617F allele burden of >50% has been associated with fibrotic transformation [25].…”

Section: Risk Factors For Survival and Leukemic Or Fibrotic Transformmentioning

confidence: 99%

“…JAK2V617F presence or increased allele burden does not appear to affect survival or leukemic transformation in PV or ET [6,25,26]. In ET, the presence of JAK2V617F has been associated with an increased risk of arterial thrombosis and a lower risk of post-ET MF [26,27].…”

mentioning

confidence: 99%

“…In ET, the presence of JAK2V617F has been associated with an increased risk of arterial thrombosis and a lower risk of post-ET MF [26,27]. In PV, a higher JAK2V617F mutant allele burden has been associated with pruritus and fibrotic transformation [25]. In general, JAK2V617F clusters with older age, higher hemoglobin level, leukocytosis, and lower platelet count [6].…”

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confidence: 99%

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Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

2015

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Disease overview: Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms, respectively characterized by erythrocytosis and thrombocytosis. Other disease features include leukocytosis, splenomegaly, thrombosis, bleeding, microcirculatory symptoms, pruritus, and risk of leukemic or fibrotic transformation. Diagnosis: PV is defined by a JAK2 mutation, whose absence, combined with normal or increased serum erythropoietin level, makes the diagnosis unlikely. Differential diagnosis in ET includes reactive thrombocytosis, chronic myeloid leukemia, and prefibrotic myelofibrosis. Janus kinase 2 (JAK2), calreticulin (CALR), or myeloproliferative leukemia virus oncogene (MPL) mutations occur in approximately 55%, 25%, and 3% of ET patients, respectively. The same molecular markers are also present in prefibrotic myelofibrosis, which needs to be morphologically distinguished from ET. Survival and leukemic/fibrotic transformation: Median survivals are ∼14 years for PV and 20 years for ET; the corresponding values for younger patients are 24 and 33 years. Life‐expectancy in ET is inferior to the control population. JAK2/CALR mutational status does not affect survival in ET. Risk factors for survival in ET and PV include advanced age, leukocytosis, and thrombosis. Leukemic transformation rates at 20 years are estimated at <10% for PV and 5% for ET; fibrotic transformation rates are slightly higher. Thrombosis risk stratification: Current risk stratification in PV and ET is designed to estimate the likelihood of recurrent thrombosis: high‐risk is defined by the presence of age >60 years or presence of thrombosis history; low‐risk is defined by the absence of both of these two risk factors. Recent data consider JAK2V617F and cardiovascular risk factors as additional risk factors. Presence of extreme thrombocytosis might be associated with acquired von Willebrand syndrome (AvWS) and, therefore, risk of bleeding. Risk‐adapted therapy: The main goal of therapy in PV and ET is to prevent thrombohemorrhagic complications. In low risk patients, this is accomplished by the use of low‐dose aspirin and phlebotomy (hematocrit target <45%) in PV. In high risk (for thrombosis) patients, treatment with hydroxyurea is additionally recommended. Treatment with busulfan or interferon‐α is usually effective in hydroxyurea failures and the additional value of JAK inhibitor therapy in such cases is limited. Screening for AvWS is recommended before administrating aspirin, in the presence of extreme thrombocytosis. Am. J. Hematol. 90:163–173, 2015. © 2014 Wiley Periodicals, Inc.

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Section: Risk Factors For Survival and Leukemic Or Fibrotic Transformmentioning

confidence: 99%

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confidence: 99%

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Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

2015

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“…The first three risk factors were then used in a three-tiered prognostic model: low risk patients (0 adverse points) displayed median survival of 26 years; intermediate risk patients (1 or 2 adverse points) displayed a median survival of 15 years; high risk patients (3 or more adverse points) displayed median survival of 8.3 years [61]. Risk factors for leukemic transformation in PV include advanced age, leukocytosis and abnormal karyotype [61] whereas JAK2V617F allele burden of >50% has been associated with fibrotic transformation [62].…”

Section: Advances In Prognosticationmentioning

confidence: 99%

Myeloproliferative neoplasms: A decade of discoveries and treatment advances

2015

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Myeloproliferative neoplasms (MPN) are clonal stem cell diseases, first conceptualized in 1951 by William Dameshek, and historically included chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). In 1960, Nowell and Hungerford discovered an invariable association between the Philadelphia chromosome (subsequently shown to harbor the causal BCR‐ABL1 mutation) and CML; accordingly, the term MPN is primarily reserved for PV, ET, and PMF, although it includes other related clinicopathologic entities, according to the World Health Organization (WHO) classification system. In 2005, William Vainchenker and others described a Janus kinase 2 mutation (JAK2V617F) in MPN and this was followed by a series of additional descriptions of mutations that directly or indirectly activate JAK‐STAT: JAK2 exon 12, myeloproliferative leukemia virus oncogene (MPL) and calreticulin (CALR) mutations. The discovery of these, mostly mutually exclusive, “driver” mutations has contributed to revisions of the WHO diagnostic criteria and risk stratification in MPN. Mutations other than JAK2, CALR and MPL have also been described in MPN and shown to provide additional prognostic information. From the standpoint of treatment, over the last 50 years, Louis Wasserman from the Unites States and Tiziano Barbui from Italy had skillfully organized and led a number of important clinical trials, whose results form the basis for current treatment strategies in MPN. More recently, allogeneic stem cell transplant, as a potentially curative treatment modality, and JAK inhibitors, as palliative drugs, have been added to the overall therapeutic armamentarium in myelofibrosis. In the current review, I will summarize the important advances made in the last 10 years regarding the science and practice of MPN. Am. J. Hematol. 91:50–58, 2016. © 2015 Wiley Periodicals, Inc.

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“…The presence of the mutation is a major criterion for PV diagnosis and it may be a prognostic marker because the burden of circulating mutated alleles (%V617F) was shown to be significantly higher in patients who developed vascular complications and in PV patients developing secondary myelofibrosis [2]. The %V617F can also be used to monitor minimal residual disease and to evaluate treatment efficacy, especially in patients treated with interferon-a [3].…”

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confidence: 99%

Lu/BCAM‐mediated cell adhesion as biological marker of JAK2V617F activity in erythrocytes of polycythemia vera patients

et al. 2015

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A prospective study of 338 patients with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications

Cited by 334 publications

References 42 publications

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

Myeloproliferative neoplasms: A decade of discoveries and treatment advances

Lu/BCAM‐mediated cell adhesion as biological marker of JAK2V617F activity in erythrocytes of polycythemia vera patients

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