Molecular characterisation of triple negative essential thrombocythaemia patients by platelet analysis and targeted sequencing

Essential thrombocythaemia (ET) is a myeloproliferative neoplasm (MPN) characterised by megakaryocyte hyperplasia and thrombocytosis. From the genetic perspective, ET patients harbour mutations in JAK2 (50–60%), CALR (15–30%) and MPL (1–5%) genes. 1 These frequencies have been determined in most studies using DNA obtained from isolated granulocytes or from whole blood, but, there is little information regarding the prevalence of these mutations when platelets are analysed. Some previous studies have reported that in ~10% of ET patients the JAK2 V617F mutation was only detectable when platelets are analysed, in agreement with the predominant involvement of the megakaryocytic-platelet lineage in this disease. 2 , 3 In contrast, some studies suggested no differences in the frequency of JAK2 V617F mutation between platelets and granulocytes when allele specific RT-PCR and RFLP analysis of platelet RNA was performed. 4 , 5 In this sense, our group has observed a higher JAK2 V617F allele burden in platelets when compared with granulocytes in ET patients, although no differences were found in the number of mutated cases. 6 Concerning mutations in MPL gene, the analysis of 82 ET patients showed in two cases the presence of MPL W515L in platelets but not in granulocytes, T-cells or erythroid colonies. 3 Finally, there is scarce information regarding the presence of CALR mutations in platelets.