ABSTRACT Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by the BCR::ABL1 translocation and usually presents with leukocytosis. While somatic mutations can occasionally occur within CML, co‐mutations in SF3B1 have rarely been reported. We describe a case of concurrent CML and MDS with mutated SF3B1 , presenting with macrocytic anemia without leukocytosis. Whole‐genome sequencing using Nanopore technology was performed to identify the t(9;22) breakpoint. Probes were designed to target the BCR::ABL1 translocation and the SF3B1 mutation. Single‐cell DNA sequencing suggested that the SF3B1 mutation likely preceded BCR::ABL1 and blunted the expected granulopoiesis, thereby explaining the myelodysplastic syndrome phenotype without leukocytosis. This case illustrates how single‐cell analysis can reveal meaningful clonal interactions that would not be evident with traditional bulk sequencing.
Brailovski et al. (Wed,) studied this question.