Matt Christopher, MD, PhD

Washington University in St.Louis

Titles + affiliations

Assistant Professor, Department of Medicine, Oncology Division
Washington University in St.Louis

Research

Resensitizing Relapsed AML Cells to the Graft-versus-Leukemia Effect after Allogeneic Hematologic Stem Cell Transplantation (HCT)

Summary

One of the most effective treatments for Acute myeloid leukemia is allogeneic hematopoietic stem cell transplantation (formerly called “bone marrow transplant.”) About 3000 patients receive these treatments each year. Unfortunately, transplants only cure patients about 40% of the time, and the main reason why transplantation fails is that leukemia relapses after the transplant. A few years ago our group performed a study of patients who relapsed after stem cell transplant. We wanted to discover what mutations or other genetic changes might happen that allows the leukemia cells to relapse. We observed a number of changes in the expression of genes that are involved in the immune system. This was intriguing, because one of the ways that transplants are believed to work is through immune pressure from the donor immune system that suppresses leukemia and the recipient. One of the important mechanisms by which donor immune cells are able to kill AML cells is by recognizing molecule called MHC class II (MHC-II) that is found on the AML cells. We discover that in 1/3 to 1/2 of cases of AML relapse after transplant, MHC-II expression has been completely lost on the relapsing AML cells. We hypothesize that without MHC-II, AML cells are no longer recognized by donor immune cells and this leads to transplant. In this grant proposal, we will uncover mechanisms by which AML cells lose MHC-II expression. In addition, we will test a new drug, a long-acting form of interferon gamma

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Leukemia Research Foundation grant
$100K awarded in 2021

Disease focus
Acute myeloid leukemia (AML)

Research focus
Relapse prevention (maintenance therapy)