Mutation profile in Indian primary myelofibrosis patients and its clinical implications

Abstract

Background: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by abnormal proliferation of megakaryocytes, bone marrow fibrosis, and extramedullary hematopoiesis. We did mutation profile of 50 patients of PMF and tried to correlate it with initial clinical presentation of these patients. Materials and Methods: All new and follow up patients who were diagnosed as PMF based on WHO 2016 definition of PMF were included. Mutation profile of these patients including JAK2 V617F, JAK2 exon 12, CALR and MPL mutations was done and all clinical, demographic and laboratory details were recorded. Results: Total 50 patients were enrolled out of which 29 were males and 21 were females. Out of these patients, 32 (64%) were JAK2 positive, 13 (26%) were CALR positive, 1 (2%) were MPL positive and 4 (8%) were triple negative. As compared to JAK2+ve patients and triple negative group, CALR positive patients were younger, had lower total leucocyte count, larger spleen size, lower dynamic international prognostic scoring system (DIPSS) score and higher grade of fibrosis of marrow. Conclusion: This study depicts that incidence of JAK2 and CALR mutations in Indian PMF patients is fairly similar to that in rest of the world. CALR positive patients have better clinical parameters at presentation and have better prognosis as compared to JAK2 positive patients.

Targeted NGS analysis of the canonical genes in 274 Indian patients with suspected myeloproliferative neoplasms: An Indian diagnostic laboratory’s perspective

“…[18][19][20] Moreover, a study in an Indian cohort of 50 PMF patients showed that 64% of the patients harbored the JAK2 V617F mutation, 26% of the patients harbored mutations in the CALR gene, and 2% in the MPL gene. 10 Of the 274 samples tested, we observed the JAK2 V617F exon 14 mutation in only 48 patients (17.5%). One plausible explanation for the low percentage of samples harboring the JAK2 V617F mutation in our cohort could be that for most of the samples referred to our lab, the hematologists performed the JAK2 V617F mutation testing elsewhere; only JAK2 V617F negative samples were referred to our lab to test for other driver mutations by the targeted NGS assay.…”

“…Therefore, the detection of these somatic mutations aids the clinician in patient management. JAK2 mutations are observed in the majority of cases in the Indian subcontinent; 10 mutations in the MPL and CALR genes account for 30-40% of Phnegative chronic MPNs. 6 Targeted capillary (or Sanger) sequencing can be used to check these mutations; however, this method is limited by its relatively low sensitivity (20%) for the detection of MPNs as certain low-depth mutations may be missed.…”