UW researchers team up to find new therapies for childhood MDS, leukemia

MADISON — Two researchers from the University of Wisconsin School of Medicine and Public Health will join forces to discover how a particular gene could affect a deadly, rare childhood genetic disease.

Drs. Emery Bresnick, professor of cell and regenerative biology and director of the UW-Madison Blood Research Program, and Inga Hofmann, assistant professor of pediatrics, will use their shared experience to better understand how regulation of the GATA-2 gene causes myelodysplastic syndrome (MDS) and leukemia.

“This work is distinct from ongoing efforts in the field and has potential to transform our understanding of MDS and leukemia and create opportunities to develop new treatments,” Bresnick said.

Hofmann, who joined the UW faculty about a year ago, brings with her a cache of knowledge as the founding principal investigator of the Pediatric MDS and Bone Marrow Failure Registry.

She created the registry while working at Boston Children’s Hospital, which is associated with Harvard Medical School. The registry, which contains hundreds of blood and bone marrow samples from patients around the United States, will provide specimens for the new joint effort with Bresnick.

Additionally, Hofmann, who is also a pediatric hematologist at UW Health, will provide a clinical perspective to the basic and translational science expertise brought by Bresnick, who specializes in research on normal and malignant blood-cell development at the Wisconsin Institutes for Medical Research.

The work will be funded by a two-year, $400,000 grant from the Edward P. Evans Foundation.

Myelodysplastic syndrome is a disease that keeps the body from properly producing enough healthy blood cells. The disease is more common in older adults, but also occurs in children and young adults.

It can develop as a low-grade disease that remains stable for many years, but in some patients it can change from that chronic state to an aggressive disease quickly leading to leukemia, and likely death, according to Hofmann.

“We want to know, ‘Does a GATA-2 mutation impact the MDS phenotype,’” she said.

It is already known that GATA-2 is involved in causing MDS, but little is known why some cases of MDS triggered by an inherited genetic change to GATA-2 lead to a low-grade disease with poorly functioning bone marrow or an aggressive disease leading to leukemia.

Transplant, the only therapy that can cure some cases of MDS, is recommended for all patients with GATA 2-related MDS. However, transplant still has its own risks as a treatment for MDS; it is associated with a high risk of toxicity, and some patients still relapse.

The goals of this study will be to predict who will get an aggressive form of the disease, to identify new strategies to treat it and to move toward individualized patient therapy, also termed precision medicine.