Pathologic Spectrum and Molecular Landscape of Myeloid Disorders Harboring SF3B1 Mutations

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• SF3B1 mutations are prevalent in myelodysplastic syndromes (MDS).
• The International Working Group for the Prognosis of MDS (IWG-PM) recently defined SF3B1-mutant MDS (SF3B1-mut-MDS) as a distinct subtype.
• Understanding the molecular landscape and prognostic implications of SF3B1 mutations is critical.

Purpose of the Study:

• To evaluate the spectrum and molecular characteristics of SF3B1-mutated myeloid disorders.
• To assess the prognostic value of SF3B1 mutations in MDS (MDS-SF3B1).
• To validate the IWG-PM classification of SF3B1-mut-MDS.

Main Methods:

• Retrospective review of 955 patients with myeloid disorders.
• Collection of clinical course, laboratory, and clinical findings via chart review.
• Classification of SF3B1-mut-MDS according to IWG-PM criteria.

Main Results:

• SF3B1 mutations were found in 75 patients, spanning various myeloid disorders.
• In MDS-SF3B1, an IPSS-R score >3 and transcription factor (TF) comutations were identified as adverse prognostic markers.
• The favorable outcome of IWG-PM-defined SF3B1-mut-MDS was confirmed, though prognostication within this subgroup was not sharply differentiated.

Conclusions:

• SF3B1 mutations are present across the spectrum of myeloid disorders.
• The favorable prognosis of IWG-PM-defined SF3B1-mut-MDS was independently validated.
• Refined prognostication within MDS-SF3B1 requires consideration of IPSS-R and TF comutations, with larger studies needed.