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

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by the BCR::ABL1 fusion gene.
• Co-mutations in CML are uncommon, with SF3B1 mutations rarely reported.
• Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders.

Purpose of the Study:

• To describe a rare case of concurrent CML and MDS with an SF3B1 mutation.
• To investigate the clonal architecture and interactions between CML and MDS drivers.
• To elucidate the mechanism behind an atypical CML presentation without leukocytosis.

Main Methods:

• Whole-genome sequencing using Nanopore technology to identify the t(9;22) breakpoint.
• Targeted probe design for BCR::ABL1 translocation and SF3B1 mutation.
• Single-cell DNA sequencing to determine clonal relationships and mutation timing.

Main Results:

• A patient presented with macrocytic anemia and features of MDS, lacking the typical leukocytosis of CML.
• Concurrent CML (BCR::ABL1) and MDS with a mutated SF3B1 were identified.
• Single-cell sequencing indicated the SF3B1 mutation preceded the BCR::ABL1 translocation.

Conclusions:

• The SF3B1 mutation likely preceded BCR::ABL1, altering granulopoiesis and causing the MDS phenotype.
• This case highlights the utility of single-cell sequencing in uncovering complex clonal interactions.
• Understanding these interactions is crucial for explaining atypical presentations in hematologic malignancies.