PHIND Seminar Series - Ravi Majeti, MD, Ph.D.

Progression of Clonal Hematopoiesis to Myeloid Malignancy 

Dr. Ravi Majeti, MD, Ph.D.
Professor of Medicine
Chief, Division of Hematology
Institute for Stem Cell Biology and Regenerative Medicine
Stanford University

Wednesday, October 16, 2019
Munzer Auditroium (B060), Beckman Center
11:00am - 12:00pm Seminar & Discussion
12:00pm - 12:15pm Reception & Light Refreshments


ABSTRACT
Myeloid malignancies are cancers of the blood lineage including myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML) with more than 40,000 new diagnoses annually in the United States. These diseases cause significant morbidity and mortality due to associated bone marrow failure leading to anemia, bleeding, and infections, and are currently treated with targeted therapies, chemotherapy, and allogeneic bone marrow transplantation. Next generation DNA sequencing has determined the spectrum of mutations associated with these cancers and has found that most cases are associated with multiple mutations that cooperate to cause disease. In our prior studies, we determined that these mutations are serially acquired in clones of self-renewing pre-cancerous/pre-leukemic blood stem cells. Separate studies analyzed blood sequencing data from large cohorts of individuals without disease and found these pre-leukemic mutations occur in the general population with increasing frequency and incidence with age. As only a minor subset of these individuals eventually progressed to develop myeloid malignancy, this entity was termed clonal hematopoiesis of indeterminate potential (CHIP). One major issue with implications for the transition from health to disease is to understand what factors influence the progression from CHIP to myeloid malignancy. In order to investigate this question, we have developed models for CHIP/pre-leukemia through the CRISPR-mediated engineering of normal human blood stem and progenitor cells. By introducing mutations in the TET2 and ASXL1 genes that are commonly mutated in CHIP, we have established models for the cell intrinsic processes of progression to myeloid malignancy and are now poised to examine cell extrinsic processes that can affect such progression. Establishing these models is key to investigating measures to eventually prevent development of myeloid malignancy.

ABOUT RAVI MAJETI
Ravi Majeti MD, PhD is Professor of Medicine, Chief of the Division of Hematology, and Member of the Institute for Stem Cell Biology and Regenerative Medicine at the Stanford University School of Medicine. He was an undergraduate at Harvard, earned his MD and PhD from UCSF, and trained in Internal Medicine at Brigham and Women’s Hospital in Boston. Dr. Majeti completed his Hematology Fellowship at Stanford, and is a board-certified hematologist. While at Stanford, he completed post-doctoral training in the laboratory of Irving Weissman, where he investigated acute myeloid leukemia (AML) stem cells and therapeutic targeting with anti-CD47 antibodies.. Dr. Majeti directs an active NIH-funded laboratory that focuses on the molecular characterization and therapeutic targeting of leukemia stem cells in human hematologic disorders, particularly AML, and has published >90 peer-reviewed articles. He is a recipient of the Burroughs Wellcome Career Award for Medical Scientists, the New York Stem Cell Foundation Robertson Investigator Award, and the Leukemia and Lymphoma Society Scholar Award. Dr. Majeti is currently a member of the Committee on Scientific Affairs for the American Society of Hematology (ASH) and serves of the editorial boards of Blood and eLife.


Hosted by: Sanjiv Sam Gambhir, M.D., Ph.D.
Sponsored by the PHIND Center