Concurrent SF3B1 Mutation and BCR::ABL1 Demonstrating a Myelodysplastic Syndrome Phenotype: A Case Report.

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.