New Medical Oncology Chair Benjamin Ebert Leads Myeloid Malignancies Research

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Benjamin Levine Ebert, MD, PhD


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In the 17 years since he joined Dana-Farber as a clinical fellow in hematology-oncology, Benjamin Ebert, MD, PhD, has made critical contributions to the understanding and treatment of hematologic disorders such as leukemia and myelodysplastic syndrome (MDS). Now, as newly appointed chair of the Institute's Department of Medical Oncology, Ebert directs more than 200 faculty members and more than 40 laboratories studying the causes of, and discovering new therapies for, a wide range of adult cancers.

In his research, Ebert has focused on uncovering the genetic mutations and mechanisms that underlie myeloid malignancies. By gaining insight into the clinical impact of genetic abnormalities in these diseases, he and his associates hope to identify new therapeutic targets and improve the identification of patients who are most likely to benefit from specific treatments.

One of Ebert's landmark discoveries has been the identification of clonal hematopoiesis of indeterminate potential (CHIP), a premalignant state occurring in about 10 percent of people before age 70. People with the condition have somatic mutations associated with leukemia in cells of the blood or bone marrow, but don't meet the criteria for a hematologic cancer diagnosis. Such individuals are at significantly elevated risk of hematologic malignancy, therapy-related leukemia, overall mortality, and, to researchers' surprise, cardiovascular disease.

The discovery of CHIP required leveraging existing exome sequencing data from tens of thousands of individuals. CHIP was found to be associated with a 10-fold increase in risk for all blood cancers.

Ebert has made important advances in a range of other areas, as well. His laboratory identified genetic predictors of outcome in patients with MDS who undergo a stem cell transplant, and whether high or moderate doses of chemotherapy are likely to be beneficial prior to transplant. He and his associates uncovered the mechanism by which the thalidomide derivative lenalidomide kills multiple myeloma cells. He was part of a team of Dana-Farber researchers who identified a distinct subtype of acute myeloid leukemia (AML) that often has a worse prognosis than other forms but is rich in targets for precision drugs.

Ebert is also co-principal investigator of a Specialized Program of Research Excellence (SPORE) in Myeloid Malignancies at the Dana-Farber/Harvard Cancer Center. Through the SPORE, he is co-leading a clinical trial of a drug that blocks a mutated gene responsible for splicing DNA, based on promising results in preclinical studies.

Dr. Ebert's current research includes studies about how particular mutations lead to CHIP or MDS, and how they might be targeted therapeutically. In addition, the Ebert Laboratory is investigating the potential of decreasing the risk of cardiovascular disease mediated by CHIP.

"One of our greatest strengths at Dana-Farber, and what makes us so unique, is that we have basic cancer biologists, translational cancer researchers, clinical researchers, and clinicians of the very highest caliber in one place," Ebert says. "As department chair, I hope to create new opportunities for working together to translate our basic research into discoveries that can change how we treat patients in the coming years."

From Nature Reviews Cancer: Clonal expansion in MDS. Early mutations tend to lead to increased haematopoietic stem cell (HSC) self-renewal, clonal expansion and the development of clonal haematopoiesis of indeterminate potential (CHIP). As the mutant clone continues to enlarge, it gives rise to an expanding population of cells in which acquisition of additional genetic or epigenetic lesions can promote progression to overt malignancy. These secondary subclonal events tend to lead to the development of overt dysplasia, myelodysplastic syndrome (MDS) and eventually secondary acute myeloid leukaemia (sAML).