PB2200 PREVALENCE OF JAK2V617F, CALR AND MPL MUTATIONS IN PATIENTS OF MYELOPROLIFERATIVE NEOPLASMS AND SPLANCHNIC VEIN THROMBOSIS IN INDIA

Abstract

Background:Recurrent somatic mutations in the JAK2, MPL, and CALR genes have been described in patients diagnosed with Philadelphia‐negative Myeloproliferative neoplasms (MPNs), including Polycythemia vera (PV), Essential thrombocythemia (ET) and Primary myelofibrosis (PMF). MPN is also the most common etiology in splanchnic vein thrombosis (SVT). MPNs account for approximately 40% of Budd Chiari syndrome (BCS) and 31% of portal vein thrombosis (PVT).The present study was aimed at studying the prevalence of JAK‐2V617F, MPLW515L/K and CALR exon 9 mutations in BCR‐ABL1 negative myeloproliferative neoplasms (MPNs) and splanchnic vein thrombosis (SVT) patients. There is paucity of such data in the Indian patients.Aims:The study had two aims: Identification of incidence of JAK2V617F, CALR exon 9 mutations and MPLW515L/K mutations in BCR‐ABL1 negative MPNs in India Identification of incidence of JAK2V617F, CALR exon 9 mutations and MPLW515L/K mutations in Indian patients of SVT MethodsA total number of 60 patients of SVT and 59 MPN patients (10 PV, 19 ET, and 30 PMF) were included in the study. The mutation analysis for JAK2V617F, CALR exon 9 and MPLW515L/K mutations were performed using the Allele specific oligonucleotide‐polymerase chain reaction (ASO‐PCR) was used to detect JAK‐2, CALR and MPL mutations.Results:Among 59 patients of MPNs and 60 SVT; JAK‐2 mutation was found in 61.0% (36/59) and 23.3% (14/60) respectively. On sub‐classification, JAK‐2 mutation was detected in 80.0% (8/10) of PV; 42.1% (8/19) of ET and 66.7% (20/30) of PMF patients.All the patients of MPNs and SVT were subjected to CALR mutation analysis. The overall rate of CALR mutations in PMF and ET was 10% (3/30) and 21.0% (4/19) respectively. Limiting the analysis to JAK2V617F negative patients of PMF and ET, it was seen that 30% (3/10) PMF and ∼36.36% (4/11) ET cases were CALR mutated. Of these 7 CALR mutations; L367fs∗46 (type‐1) and K385fs∗47 (type‐2) mutations were found in 5 and 2 patients respectively. MPL mutation was identified in 5.26% (1/19) ET cases. Triple negative ET and PMF were ∼31.5% (∼6/19) and ∼23.3% (7/30) respectively. None of the SVT patients were observed to be CALR mutated and none showed the MPLW515L/K mutations.Summary/Conclusion:Indian patients exhibit a lower incidence of CALR mutations in Primary myelofibrosis than that seen in the western literature. However, the incidence of CALR mutations is the same as that reported earlier in Indian patients of Essential thrombocythemia. Triple negative cases constitute 31.5% of all cases of Essential thrombocythemia and 23.3% of Primary myelofibrosis Indian patients show a Testing for CALR mutations and MPLW515L/K mutations in splanchnic vein thrombosis is not justified.