Potential New Therapy for Myelodysplastic Syndromes

Research Brief

Potential New Therapy for Myelodysplastic Syndromes

Body

Myelodysplastic syndromes (MDS) and other blood cancers arise from mutations in hematopoietic stem and progenitor cells (HSPCs), which generate new blood cell populations throughout a person’s life. Some cases of MDS can be traced to HSPC mutations affecting splicing factor SF3B1, a protein needed to splice pre-messenger RNA into mRNA molecules. But how splicing factor defects alter HSPC function is not well understood.

In a study involving zebrafish published December 13 in Cell Reports, Teresa V. Bowman, Ph.D., and colleagues found that, in order to spur HSPC dysfunction in MDS, defective splicing depends heavily on the transcription factor STAT3. Using blood from MDS patients, the researchers showed that STAT3 inhibitors selectively kill HSPCs that contain splicing-factor mutations. MDS treatments have changed little in the past 20 years, and these findings suggest that STAT3 inhibitors could benefit this patient population.

Dr. Bowman is an associate professor of developmental & molecular biology, oncology, and medicine at Einstein and a member of the Montefiore Einstein Cancer Center (MECC). Dr. Verma is a professor of oncology, medicine, and developmental & molecular biology at Einstein and director of the Myelodysplastic Syndromes (MDS) Program at MECC. Dr. Shastri is an associate professor of oncology, medicine, and developmental & molecular biology at Einstein and an oncologist at MECC.