Rafael Bejar

Assistant Professor

Our lab is focused on understanding the genetic changes that drive the development and progression of hematologic malignancies like acute myeloid leukemia and myelodysplastic syndromes. Our goal is to translate our discoveries into clinically meaningful improvements in how we care for patients with these disorders.

Our prior work helped characterize the range of genetic alterations that exist in patients with myelodysplastic syndromes (MDS). We studied bone marrow sample from over 400 patients with these disorders and examined them for mutations in over 20 recurrently mutated genes. We learned about the relative frequency of these mutations, how they can overlap with each other, and how they may better classify molecular subtypes of MDS. We demonstrated that mutations in several genes are associated with clinical features seen in patients with MDS, potentially explaining much of the heterogeneity associated with this disease. Most importantly, we identified mutations in several genes, that when present, are associated with a poorer prognosis than would otherwise be predicted using standard clinical scoring systems. This has helped accelerate the drive to include tumor sequencing in the standard evaluation of patients with MDS.

Currently we are investigating how acquired mutations in the diseased cells from patients with myelodysplastic syndromes are associated with their response to treatment with drugs like azacitidine and decitabine. We hope to discover genes that physicians can test for mutations in order to select the best treatment options for their patients with MDS. These studies should also give us insight into the mechanisms of drug resistance and how we may be able to overcome them.

In addition, we are interested in the functional consequence of the mutations we have characterized in patients with MDS. For example, we are studying how mutations in the EZH2 gene, which are associated with a poor prognosis, might affect the function neutrophils in patients with these abnormalities. 

Going forward, we plan to implement clinical sequencing of bone marrow specimens from patients with MDS and related hematologic malignancies. Our plan is work out how best to use this information to personalize the choice of therapy and overall care of our patients with these disorders.

Benjamin Ebert, David Steensma, Guillermo Garcia Manero, and their colleagues at the Brigham and Women’s Hospital, the Dana-Farber Cancer Institute, and the MD Anderson Cancer Center – Examination of mutations that may predict response to hypomethylating agents in patients with MDS.
Nancy Huang and Anjana Rao – La Jolla Institute for Allergy and Immunology – Examination of 5-hydroxymethycytosine in MDS.
Derek Murphy and Mike Makrigiorgos – Dana-Farber Cancer Institute – High sensitivity methods for detecting rare, but clinically important mutations.

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