August 1, 2019

Grant bolsters research on myelodysplastic syndromes

Michael Savona, MD, has received a competitive grant to develop therapies for patients with myelodysplastic syndromes.

Michael Savona, MD, professor of Medicine and Cancer Biology, and director of Hematology Research at Vanderbilt- Ingram Cancer Center, has received a competitive grant award from the Edward P. Evans Foundation.

Michael Savona, MD

The Discovery Research Grant (DRG) will support his work to develop therapies for patients with myelodysplastic syndromes, a group of cancers that occur when immature blood cells in the bone marrow don’t fully develop or fail to become healthy blood cells.

The grant, which totals $400,000 over two years, is his second consecutive DRG from EvansMDS, an initiative of the Edward P. Evans Foundation to support research in myelodysplastic syndromes (MDS).

The prior award supported research involving the role of the MCL1 protein, which when overexpressed can promote the survival of cancer cells.

Savona explored whether MCL1 could be better controlled by combining an experimental drug that was developed by Stephen Fesik, PhD, Orrin H. Ingram II, Professor of Cancer Research, and colleagues, with other drugs in MDS.

Results from leukemia cell lines and patient sample studies conducted by Savona and colleagues, reported in Cancer Discovery last fall, indicated the combination inhibited MCL1 as well as BCL2, another protein that promotes cancer cell survival. The cell line studies involved acute myelogenous leukemia (AML), a blood cancer that commonly follows MDS diagnoses. Savona opted to use AML cells due to the difficulty of maintaining MDS cells.

The new award from EvansMDS will help Savona address that difficulty. It supports the creation of organoids with a microenvironment for MDS cell survival.

“It’s really hard to study MDS in the laboratory,” Savona said. “To develop new therapies for MDS, we have to come up with a new system to study how drugs can affect cells in MDS that keep patient samples alive long enough to do this.

“If you try to take cells from the bone marrow of a patient with MDS and study them in a dish in vitro, they die within 72 hours — just because it is in a bone marrow failure state, and the cells are not as robust.”

Savona and colleagues have already had some success in the lab extending MDS cell survival, but they haven’t reported those results as they work to replicate those experiments and quantify their implications.

Vanderbilt scientists have multiple lines of ongoing inquiry to better understand MDS and develop potential therapies for the blood cancers. The Edward P. Evans Foundation is a major funder of that research and has provided over $4 million for those initiatives at Vanderbilt.

“The EvansMDS initiative is the single most important MDS-specific grant funding mechanism,” Savona said. “It is very scientifically driven. With what EvansMDS has done, more MDS-related discoveries have occurred in the last couple years than in the last several decades based on the funding and the collaborations it has created.”