Clonal evolution in chronic myelomonocytic leukemia treated with hypomethylating agents

Chronic myelomonocytic leukemia (CMML) is a complex myeloid neoplasm with limited therapeutic options and poor prognosis. Somatic mutation burden has been shown to remain unaltered despite response to hypomethylating agents (HMAs), but little is known about clonal evolution on HMA therapy. We studied clonal architecture and evolution in clinically annotated CMML patients treated with single-agent 5-azacitidine. We genotyped longitudinal pairs of leukemic and constitutional control samples by whole exome sequencing, then reconstructed clonal structures based on copy number and somatic variants using a customized computational algorithm.