Significance of Somatic Mutation Profiling in CML Beyond BCR-ABL: A Retrospective Study of the Indian Population

Somatic mutation and fusion detection in acute myeloid leukemia to determine disease subtype and treatment regime is a common practice, but it’s not yet employed in chronic myeloid leukemia (CML). CML is still monitored by routine quantitative determination of the BCR-ABL fusion transcript and treated with tyrosine kinase inhibitors (TKIs). Despite the availability of the three generations of TKIs, resistance and progression in CML pathogenesis suggest a strong role for somatic mutations. The present study aimed to identify the role of somatic mutation profiling in CML patients in disease management. 196 CML patient samples were used in this investigation, comprising 26 CML-BP, 8 CML-AP, and 162 CML-CP samples. Following cytogenetic analysis for confirmation, each sample was sequenced utilizing the Ion Torrent platform by a targeted panel. Of the 196 CML samples, 81 (41.33%) had 125 variations affecting 27 genes, while 115 (58.67%) harboured no mutations. The study revealed that ASXL1 (31.2%), ABL1 (14.4%), and TET2 (8.8%) were the most frequently altered genes. These genes are recognized indicators of CML disease. Few samples found with mutated GATA2, IDH1, NRAS, SETBP1, WT1, PHF6, KIT, etc. and fusions like RUNX1(5)-MECOM (2) and CBFB- MYH11 are indicative of disease progression. The outcome of this study suggests that mutational profiling of CML patients can help in the prognostication of disease. Based on the results of the study, the authors have also provided possible future risk stratification and diagnosis workflow for CML disease.