Mapping the Mutational Landscape of Myeloproliferative Neoplasms: An Indian Cohort of 1,000 Patients

Abstract

Abstract Introduction Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by overproduction of myeloid lineages. Driver mutations in JAK2 , CALR , and MPL account for most cases; however, additional somatic mutations contribute to disease heterogeneity, prognosis, and therapeutic response. Next-generation sequencing (NGS) enables comprehensive genomic profiling of these alterations. Objectives This article ails to characterize the mutational landscape of MPNs in a large Indian cohort using targeted NGS. Materials and Methods A total of 1,000 patients with clinically suspected MPNs were analyzed using DNA- and RNA-based NGS assays. Genomic DNA from peripheral blood or bone marrow samples underwent targeted library preparation and sequencing on Illumina and Thermo Fisher platforms. Bioinformatic analysis identified single-nucleotide variants, insertion–deletions, and clinically relevant gene fusions. Results Somatic alterations were detected in 490 patients. JAK2  V617F was the most frequent mutation (256 cases; 52.9%), followed by CALR exon 9 indels (50 cases; 11.1%) and MPL mutations (24 cases; 5.3%). Rare JAK2 exon 12 variants were identified in seven cases. Additional mutations included TET2 (94 cases; 20.9%), ASXL1 (53 cases; 11.8%), and SRSF2 (44 cases; 9.8%). RNA sequencing detected clinically relevant fusions including BCR::ABL1 , FIP1L1::PDGFRA , and ETV6::PDGFRB . Conclusion This large NGS-based study highlights the genetic heterogeneity of MPNs in an Indian population and supports the clinical utility of integrated genomic profiling for molecular diagnosis and risk stratification.