SF3B1 mutated MDS: Blast count, genetic co-abnormalities and their impact on classification and prognosis

Area of Science:

• Hematology
• Genomics
• Oncology

Background:

• Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell disorders.
• A distinct MDS entity with SF3B1 mutations and <5% blasts was recently proposed, suggesting a favorable prognosis.
• Further characterization of this entity's genomic landscape and clinical outcomes is needed.

Purpose of the Study:

• To analyze the genomic landscape of MDS patients with SF3B1 mutations.
• To evaluate the acute myeloid leukemia (AML) transformation rate and clinical outcomes for the proposed SF3B1-mutated MDS entity.
• To identify prognostic factors influencing survival in SF3B1-mutated MDS.

Main Methods:

• Whole genome sequencing of 734 MDS patients.
• Classification of patients based on SF3B1 mutation status and adherence to the proposed SF3B1 entity criteria.
• Analysis of AML transformation rates, survival data, and accompanying mutations.
• Multivariate analysis to identify independent prognostic factors.

Main Results:

• SF3B1 mutations were found in 31% of patients, often co-occurring with TET2 mutations.
• Patients meeting the SF3B1 entity criteria (SF3B1ent) exhibited longer survival and lower AML transformation rates compared to SF3B1-mutated patients not meeting the criteria (SF3B1nent).
• RUNX1 mutations and del(5q) were identified as independent negative prognostic factors for overall survival.

Conclusions:

• MDS with SF3B1 mutations, particularly those meeting the proposed entity criteria, demonstrates a favorable prognosis.
• The prognosis is independent of blast count when karyotype and RUNX1 mutations are considered.
• SF3B1-mutated MDS has a lower AML progression risk, especially when lacking adverse genetic alterations.