JAK2 V617F, MPL, and CALR Mutations in Essential Thrombocythaemia and Major Thrombotic Complications: A Single-Institute Retrospective Analysis

Abstract

Thrombo-haemorrhagic events are the main cause of morbidity and mortality in essential thrombocythemia. The aim of this study was to estimate the incidence of thrombotic events and the impact of the JAK2V617F, MPL (W515L, W515K, W515R, W515A and S505N) and CALR (type-1, type-2) mutations on 101 essential thrombocythaemia patients (72 females and 29 males with a mean age of 61 years) diagnosed in a Southern Hungarian regional academic centre. The incidence of major thrombosis was 13.86 %. Sixty percent of the patients carried the JAK2V617F mutation. The MPL mutations were analysed by sequencing and the W515L was the only one we could identify with an incidence of 3.96 %. Type-2 CALR mutation could be identified in 3 cases among the patients who had JAK2/MPL-unmutated ET. Statistical analyses revealed that the JAK2V617F mutation was associated with significantly increased levels of platelet (p = 0.042), haemoglobin (p = 0.000), red blood cell (p = 0.000) and haematocrit (p = 0.000) and hepatomegaly (p = 0.045) at diagnosis compared to JAK2V617F negative counterparts, however there was no significant association between the JAK2V617F mutation status (relative risk: 1.297, 95 % CI 0.395-4.258; p = 0.668) and subsequent thrombotic complications. The impact of JAK2V617F, MPL W515L and CALR mutations on the clinical findings at the diagnosis of ET was obvious, but their statistically significant role in the prediction of thrombotic events could not be proven in this study. Our results indirectly support the concept that, besides the quantitative and qualitative changes in the platelets, the mechanisms leading to thrombosis are more complex and multifactorial.

Association Between Soluble CD40L with Thrombosis Occurrence and JAK2 V617F Mutation in Essential Thrombocythemia

“…However, the present study results indirectly support the concept that the JAK2V617F mutation contributes to intrinsic changes in both megakaryocyte and platelet biology beyond the increase in cell numbers [35][36][37]. The results of another single center analyses also revealed that the JAK2 V617F (−) cases did not differ significantly from the JAK2 V617F (+) cases in the incidence of thrombosis [38][39][40]. The number of involved patients might be determinative in view of clear evaluation of the predictive value of the JAK2 V617F mutation in thrombosis [41,42].…”

Correlation analysis between JAK2, MPL, and CALR mutations in patients with myeloproliferative neoplasms of Chinese Uygur and Han nationality and their clinical characteristics

“…However, another study detected both JAK2 V617F and CALR mutations in a small number of patients, as well as both JAK2 V617F and MPL W515L/S mutations. 21 Any correlation among the three mutations in MPN patients remains to be identified.Interestingly, the age of the JAK2 -mutant group was significantly higher than the CALR -mutant group and the JAK2 , CALR non-mutation group in both Han and Uyghur populations. This supports the fact that age, but not nationality, is the key factor associated with JAK2 mutation rate, and is consistent with previous findings.…”

CALR mutations screening in wild type JAK2V617F and MPLW515K/L Brazilian myeloproliferative neoplasm patients

“…Since CALR mutations discovery, several studies have been correlated these mutations with clinical data and patient outcome in MPN [14][15][16][17][18][19][20][21][22][23][24]. Interestingly, it was described the presence of CALR mutation in peripheral granulocytes of two PV patients negative for both JAK2 V617F and JAK2 exon12 mutations [25].…”