$1.2 million NIH grant may help unravel the interplay between Down syndrome and myeloid leukemia

A four-year, $1.2 million grant from the National Cancer Institute of the National Institutes of Health may help researchers find new clues to the interplay between Down syndrome (DS) and myeloid leukemia (ML).

Jeffrey Taub, M.D., professor of pediatrics and Yubin Ge, Ph.D., professor of oncology in Wayne State University's School of Medicine, will use this funding to develop a novel strategy to enhance the antileukemic activity of the chemotherapy drug cytarabine against myeloid leukemia associated with DS.

Children with DS are known to have a significantly higher risk of developing acute leukemias compared to children without it. The goal of this study is to identify a novel treatment strategy of enhancing cytarabine treatment to further improve patient outcomes and prevent/reduce relapses with ML-DS patients.

There are some very unusual findings in children with DS who have leukemia. Why is it when children get this, it is usually highly curable, but there are other patients, including children, who are difficult to cure and whose leukemia can often relapse? We want to know why it can be so resistant to treatment in certain patients."

Jeffrey Taub, M.D., professor of pediatrics, Wayne State University's School of Medicine

"There is an emphasis on this as a team collaboration," said Ge. "Dr. Taub is a physician who works with patients, and I am a basic scientist who directs the lab work. The team aspect of this is very important. I am extremely grateful for the hard work of other members of our research team, Dr. Lisa Polin, Dr. Sijana Dzinic, Dr. Wei Chen, Holly Pitman, Jianlei Zhao, Jenna Thibodeau, Jay Kushner, and Kathryn White, which was critical for the success of securing this award. I am also grateful for the institutional support from the Department of Oncology, the Karmanos Cancer Institute and the Wayne State University School of Medicine, especially Ms. Valerie Wade, who helped with the submission as well as the pre-award process."

Taub and Ge will test different drug treatments on ML-DS cells to identify new treatments that prevent or delay ML-DS relapse, which should prolong ML-DS patient survival.

"There are very few people looking at children with DS and leukemia," said Taub. "From a pharmacology standpoint, some of our work has focused on asking what it is about DS -;where these individuals who have three copies instead of two copies of chromosome 21 -; that might be affecting how leukemia functions in their bodies. We are seeing if proteins are being produced as a result or how that gene is being expressed at higher levels. We want to continue to find out why some patients respond well to treatment and to see if there is any new intervention we can perform in the subset of patients who tend to relapse in their leukemia. Are there new strategies we can try from the very beginning that could prevent that relapsing or stop patients who are currently relapsing?"

"DS people are a vulnerable population," said Ge. "What we are doing is focusing on children with DS who have myeloid leukemia. Children with DS have a significant chance of contracting the disease, but they also have higher chances of beating it. Some among them have a higher chance of the myeloid leukemia relapsing. Once it relapses, it is often too late to get the patient back into remission. We want to prevent or delay the reoccurrence of the disease."

"This grant is an excellent example of the important research happening at Wayne State University that has the potential to impact the lives of many," said Ezemenari M. Obasi, Ph.D., Wayne State's vice president for research & innovation. "Drs. Taub and Ge's collaborative work will aim to find new treatments and further our knowledge of leukemia and Down syndrome that ultimately may help countless children live longer, healthier lives."

The award number for this grant from the National Cancer Institute of the National Institutes of Health is 1R01CA290480.