Clinical significance of V617F mutation of the JAK2 gene in patients with chronic myeloproliferative disorders

Basquiera, Ana Lisa; Soria, Néstor Walter; Ryser, Ricardo; Salguero, Miriam; Moiraghi, Beatriz; Sackmann, Federico; Sturich, Ana Gabriela; Borello, Adriana; Berretta, Adriana; Bonafe, M. García; Barral, José M.; Palazzo, E; Garcı́a, Juan José

doi:10.1179/102453309x12473408860226

Cited by 33 publications

(23 citation statements)

References 28 publications

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“…Campbell et al [13] [15]. Several studies have shown that the prevalence of the JAK2 V617F mutation in ET is ranging approximately from 23 to 69 % [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. In the present study, the frequency of JAK2 V617F mutation positive was 46 % in ET, which is consistent with the studies in the literatures.…”

Section: Discussionsupporting

confidence: 95%

Evaluation of clinical and laboratory findings with JAK2 V617F mutation as an independent variable in essential thrombocytosis

et al. 2014

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Essential thrombocythemia (ET) is an entity of classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), characterized by thrombocytosis with megakaryocytic hyperplasia and thrombocytes are increased with abnormal functions. Discovery of the protein tyrosine kinase JAK2 V617F allele contributed to better understanding of the pathogenetic mechanisms of MPNs. Acquired single point mutation in the JAK2 V617F was determined approximately 50-60 % of patients with ET. In this study we aimed to investigate the relationship between JAK2 V617F gene mutation, hematologic, biochemical markers and the complications in the ET patients. A total of 268 patients diagnosed with ET and 219 of those studied for JAK2 gene mutation were followed at the hematology clinics of three major hospitals between 2008 and 2013 were screened retrospectively. Laboratory, clinical and hematologic parameters were compared for JAK2 V617F positive and JAK2 V617F negative patients with ET. 102 (46 %) patients were positive with the JAK2 V617F mutation. The complications were observed in 61 (28 %) patients and 38 (62 %) of them had JAK2 V617F mutation. The levels of white blood cells, neutrophil, basophil, red blood cells, hemoglobin, hematocrit, mean platelet volume, thrombocytes, eosinophil; urea, creatinine were significantly different in patients with the JAK2 V617F mutation (P < 0.05). Presence of the JAK2 V617F mutation supports the diagnosis of ET. It would be useful to investigate the JAK2 V617F mutation and the hematologic and biochemical markers at diagnosis with respect to consider the risk of developing complications and to take the precautions against these complications.

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Section: Discussionsupporting

confidence: 95%

Evaluation of clinical and laboratory findings with JAK2 V617F mutation as an independent variable in essential thrombocytosis

et al. 2014

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“…From previous reports, megakaryopoiesis was enhanced when the progenitors are heterozygous for JAK2 V617F, whereas erythropoiesis is strongly stimulated when the progenitors are homozygous for the JAK2 V617F mutation [19]. In this study, patients with the JAK2 V617F mutation had an increased platelet count compared to those with wild-type JAK2, which was consistent with the results of a previous study [20]. These data suggest that the pathogenesis of thrombocytosis in patients with these 4 diseases might be similar to that in the case of essential thrombocytosis.…”

Section: Discussionsupporting

confidence: 92%

JAK2 V617F mutation in myelodysplastic syndrome, myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable, refractory anemia with ring sideroblasts with thrombocytosis, and acute myeloid leukemia

et al. 2010

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BackgroundThe JAK2 V617F mutation has been noted in the cases of polycythemia vera, essential thrombocythemia, and primary myelofibrosis patients. This mutation occurs less frequently in acute myeloid leukemia (AML) and other hematologic diseases, such as myelodysplastic syndrome (MDS); myelodysplatic syndrome/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U); and refractory anemia with ring sideroblasts with thrombocytosis (RARS-T).MethodsPatients diagnosed with hematologic diseases other than MPN who visited Seoul St Mary's Hospital from January 2007 to February 2010 were selected. A total of 43 patients were enrolled in this study: 12 MDS, 9 MDS/MPN-U, 7 RARS-T, and 15 AML patients. The diseases were diagnosed according to the 2008 WHO classification criteria. Data obtained from JAK2 V617F mutation analysis and cytogenetic study as well as complete blood count and clinical data were analyzed.ResultsOf the 43 patients, 6 (13.9%) harbored the JAK2 V617F mutation. The incidence of the JAK2 V617F mutation in each patient group was as follows: 8.3% (1/12), MDS; 22.2% (2/9), MDS/MPN-U; 14.3% (1/7), RARS-T; and 13.3%, (2/15) AML. The platelet count was higher than 450×109/L in 3 of the 6 patients (50%) harboring the JAK2 V617F mutation, and it was in the normal range in the remaining 3 patients. Among the 6 patients, 1 MDS and 1 MDS/MPN-U patients had the 46,XX,del(20)(q11.2) karyotype.ConclusionThe JAK2 V617F mutation is associated with an increased platelet count in MDS, MDS/MPN-U, RARS-T, and AML patients. Cytogenetic abnormalities of del(20)(q11.2) occurred in 1/3 of patients with the JAK2 V617F mutation but further studies are required to confirm this association.

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“…In another study for ET patients [21], no significant difference was found for WBC counts in the mutated and wild-type groups. However, Ana L. Basquiera et al [22] reported that WBC counts and Hb were significantly higher in JAK2 V617F mutated group than that in wild-type group in ET and PV patients, but platelet counts showed no significant difference. Therefore, the relationship between JAK2 V617F and hemogram variation was controversial, and no investigation has been performed to determine the JAK2 V617F mutation rate in patients groups classified by RBC counts, WBC counts, platelet counts and lineage hyperplasia state.…”

Section: Introductionmentioning

confidence: 94%

Impact of JAK2 V617F Mutation on Hemogram Variation in Patients with Non-Reactive Elevated Platelet Counts

Zhou

Zeng

et al. 2013

PLoS ONE

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BackgroundNon-reactive platelet counts elevation occurs mainly in myeloproliferative disorders (MPDs), which have been reported to be closely associated with JAK2 V617F mutation. Complete blood cell count (CBC) is essential in diagnosis of MPDs, however, the impact of JAK2 V617F mutation on the patients’ hemogram variation remains not clear.MethodsJAK2 V617F mutation was detected by allele specific real-time quantitative fluorescence PCR (AS-qPCR).ResultsOf the 402 non-reactive platelet elevating patients, JAK2 V617F mutation was detected in 222 (55.2%) patients. RBC counts, WBC counts, platelet-large contrast ratio (P-LCR), platelet distribution width (PDW) and mean platelet volume (MPV) were much higher in JAK2 V617F mutated patients, except platelet counts. In addition, when the patients were classified into subgroups by blood cell counts, it was found that JAK2 V617F mutation rate increased progressively with the increase of RBC counts and WBC counts, other than platelet counts. Furthermore, trilineage hyperplasia group showed highest JAK2 V617F mutation rate (93.26%), followed by the bilineage hyperplasia groups. Lastly, JAK2 V617F mutant allele burden was found much higher in polycythemia vera (PV) patients [median(P25–P75): 45.02%(35.12%–54.22%)] than in essential thrombocythemia (ET) patients [median(P25–P75): 28.23%(17.77%–41.66%)], and that it increased with WBC counts (r = 0.393, p = 0.000) and RBC counts(r = 0.215, p = 0.001), other than platelet counts (r = −0.051, p = 0.452). Further analysis revealed that in ET patients, JAK2 V617F mutant allele burden correlated with WBC counts and platelet counts positively, other than RBC counts, while in PV patients, it correlated with WBC counts and RBC counts positively, but not platelet counts.ConclusionsJAK2 V617F mutation occurs frequently in patients with non-reactive elevated platelet counts. The presence of JAK2 V617F mutation has great impact on hemogram variation, including RBC counts, WBC counts, platelet parameters and lineage hyperplasia, but not on platelet counts. Besides, JAK2 V617F mutant allele burden affects the blood cell proliferation pattern.

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Clinical significance of V617F mutation of the JAK2 gene in patients with chronic myeloproliferative disorders

Abstract: We found an association between JAK2 V617F and thrombotic events in patients with PV and ET.

Cited by 33 publications

References 28 publications

Evaluation of clinical and laboratory findings with JAK2 V617F mutation as an independent variable in essential thrombocytosis

Evaluation of clinical and laboratory findings with JAK2 V617F mutation as an independent variable in essential thrombocytosis

JAK2 V617F mutation in myelodysplastic syndrome, myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable, refractory anemia with ring sideroblasts with thrombocytosis, and acute myeloid leukemia

Impact of JAK2 V617F Mutation on Hemogram Variation in Patients with Non-Reactive Elevated Platelet Counts

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