Dr. Abdel-Wahab [Edward P. Evans Foundation Clinical Investigator] specializes in specific blood cancers called myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). He recently identified mutations in the gene ASXL1 in patients with MDS and AML. ASXL1 is one of the most commonly mutated genes in MDS patients, and these mutations occur in up to 20% of AML patients. ASXL1 mutations result in a worsened overall survival in MDS and AML patients and contribute to chemotherapy resistance in AML. However, exactly how these mutations contribute to leukemia development remains unknown.
He has demonstrated that loss of ASXL1 results in increased expression of genes that are known to promote development of AML. Preliminary data suggests that ASXL1 regulates expression of key genes by affecting proteins called histones. In a mouse model, loss of ASXL1 alone results in a phenotype remarkably similar to human MDS. Moreover, when ASXL1 loss is combined with other genes known to promote chronic leukemia in mice, an acute leukemia develops that hastens death of the mice. His overall goal is to gain a more thorough understanding of ASXL1 function and to ultimately test approved as well as novel targeted therapeutics for treatment of MDS and AML.
