Matthew J. Walter, MD | Aplastic Anemia and MDS International Foundation

Matthew J. Walter, MD

Lead Photo
The role of U2AF1 mutations in the pathogenesis of myelodysplastic syndromes
Original Research Center: 
Washington University in St. Louis
Pubmed Author Name: 
Walter MJ
Current Position/Title: 
Assistant Professor Department of Medicine Oncology Division, Stem Cell Biology Section, Department of Genetics

The genes responsible for MDS initiation are largely unknown. Recently, a group of genes that are important for splicing together RNA in cells were found to be mutated in up to 57% of MDS patients. How these mutations contribute to MDS initiation is unknown. We will determine whether a mutation in one of these genes (U2AF1) affects blood cell formation in mice and alters the splicing of RNA in bone marrow cells from mice and MDS patients.

2012
First Year Report: 

Myelodysplastic syndromes (MDS) are blood cell diseases associated with life threatening infections and bleeding and can evolve to leukemia. Approximately 20,000 adults will be diagnosed with MDS each year and the associated mortality is high. We know that gene mutations occur in bone marrow cells from patients with MDS that are acquired sometime during their lifetime, but it remains largely unknown which gene mutations are responsible for MDS initiation. Recently, a group of genes that are important for splicing together RNA in cells were found to be mutated in up to half of MDS patients. How these mutations contribute to MDS initiation is unknown. We are studying a mutation in one of these genes (U2AF1) to determine how it alters blood cell formation and development. We observed that certain types of blood cells are affected more than others in young mice expressing the mutant gene and immature blood cells are increased. We are continuing to study these mice as they get older and will try to understand why blood cell development is abnormal. A better understanding of how U2AF1 mutations contribute to MDS development may uncover approaches that could be used to eliminate cells carrying these mutations in patients with MDS.

Final Report: 

Myelodysplastic syndromes (MDS) are blood cell diseases associated with life threatening infections and bleeding and can evolve to leukemia. Approximately 20,000 adults will be diagnosed with MDS each year and the associated mortality is high. We know that gene mutations occur in bone marrow cells from patients with MDS that are acquired sometime during their lifetime, but it remains largely unknown which gene mutations are responsible for MDS initiation. Recently, a group of genes that are important for splicing together RNA in cells were found to be mutated in up to half of MDS patients. How these mutations contribute to MDS initiation is unknown. We are studying a mutation in one of these genes (U2AF1) to determine how it alters blood cell formation and development in mice. We observed that mice expressing the mutant U2AF1 gene have low white blood cell counts, similar to that seen in MDS patients. Mutant mouse expressing bone marrow cells also have changes in splicing of their RNA that are identical to bone marrow cells from MDS patients.  Future studies will focus on how we could be use this mouse model to develop approaches to target cells carrying these mutations in patients with MDS.

Current Institution: 
Washington University in St. Louis

Matthew Walter, M.D. of Washington University in St. Louis, a 2005 AA&MDSIF grantee, credited his grant from AA&MDSIF as the start of his research into the genomics of MDS. Dr. Walter and his colleagues recently published the results of their significant work in the New England Journal of Medicine. Watch his interview on the AA&MDSIF YouTube channel.