New Insights into Myelodysplastic Syndrome Pathogenesis

A recurring mutation in SF3B1, the gene encoding RNA splicing factor 3B, was identified in MDS with ring sideroblasts.

Myelodysplastic syndrome (MDS) is a complex group of bone marrow failure disorders with a clinical spectrum ranging from asymptomatic cytopenias to acute leukemia transformation. To identify acquired genetic mutations in MDS, investigators performed massively parallel sequencing to compare malignant cells from marrow or peripheral blood with constitutional DNA from normal lymphocytes or buccal mucosa.

A total of 64 acquired mutations in MDS cells were identified from nine patients. Six of these patients had recurring mutations in SF3B1, which encodes a component of the RNA “splicosome” that is essential to normal messenger RNA processing. Further testing by SF3B1 gene sequencing revealed that 72 (20%) of 354 MDS patient cell samples harbored…

Reviewing Author

Michael E. Williams, MD

Disclosures

Consultant/Advisory BoardAbbVie; AstraZeneca; Beigene; Janssen; Pharmacyclics

Grant/Research SupportJanssen

Editorial BoardsAmerican Board of Internal Medicine (ABIM) Hematology Longitudinal Knowledge Approval Committee

Michael E. Williams, MD

Disclosures

Consultant/Advisory BoardAbbVie; AstraZeneca; Beigene; Janssen; Pharmacyclics

Grant/Research SupportJanssen

Editorial BoardsAmerican Board of Internal Medicine (ABIM) Hematology Longitudinal Knowledge Approval Committee