Related Experiment Video
Updated: Apr 18, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Concurrent SF3B1 Mutation and BCR::ABL1 Demonstrating a Myelodysplastic Syndrome Phenotype: A Case Report
Eugene Brailovski1, Amirali Vahedi2, Véronique Lisi3
1Jewish General Hospital McGill University Montreal Quebec Canada.
Insights
This study details a rare case of chronic myeloid leukemia (CML) with a co-occurring SF3B1 mutation, presenting as myelodysplastic syndrome without leukocytosis. Single-cell sequencing revealed the SF3B1 mutation likely preceded BCR::ABL1, impacting granulopoiesis.
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.
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.
