Hollings Cancer Center researcher awarded NCI grant to pursue early investigator studies in leukemia

MUSC Hollings Cancer Center researcher Haizhen (Jen) Wang, Ph.D., was awarded a five-year $344,000 per year grant by the National Cancer Institute (NCI) to pursue her early investigator studies in leukemia.

Wang, assistant professor in the Department of Cell and Molecular Pharmacology and Experimental Therapeutics, originally submitted the grant as a traditional R01 application. "I was thrilled when I found out that my grant was well received, and the funding mechanism was converted to the more desirable R37. An R37 is more prestigious because of the time extension option. This allows significant time to develop my research while also growing a new lab," she said.

Understanding the intricate biological communication between cancer cells and a patient's healthy cells helps to improve treatment options. Wang's research focuses on uncovering the connection between cancer metabolism and cancer immunology. Her research has shown that a molecule called cyclin-dependent kinase 6 (CDK6) may be a key regulatory molecule in cancers such as leukemia.

T-cell acute lymphoblastic leukemia, an aggressive cancer of the immune cells in the blood, has a less than 25% overall survival rate for relapsed disease. Cancer progression occurs when the cancerous T-cells infiltrate, or disseminate, into the organs. Leukemia cell dissemination is one of the main causes of cancer relapse and patient mortality.

One of the goals of my research is to figure out how to use the immune system to reduce leukemia progression. We do not know how the leukemia T-cells escape detection by the patient's healthy immune cells. The goal of the grant is to test whether inhibiting CDK6 could be a therapeutic treatment strategy to stop the dissemination of T-cell leukemia."

Haizhen (Jen) Wang, Ph.D., MUSC Hollings Cancer Center Researcher

The findings that were published in August in The Journal of Clinical Investigation provided the preliminary data that led to the grant funding. Wang demonstrated that CDK6 plays an important role in T-cell leukemia.

"My initial work showed that the protein kinase CDK6 has much higher activity in T-cell acute lymphoblastic leukemia. This is because the inhibitor proteins that reduce CDK6 activity are mutated in more than 50% of the patients. We think that blocking the CDK6 kinase activity may prevent leukemia cell proliferation, induce cell death and stop dissemination," said Wang.

Wang found that increased CDK6 activity turned on another molecule called PFKP, which promotes leukemia T-cell dissemination into the bone marrow, spleen and liver. Samples from patients showed increased PFKP in invasive cancers but not in nonmalignant lymph nodes. The presence of nuclear PFKP in these patient samples correlated with poor survival in the T-cell leukemia patients. The research team hopes that nuclear PFKP may be a prognostic marker to identify the most aggressive T-cell leukemia cases.

The project funded by the R37 grant will expand on this initial data. First, Wang's team will study how CDK6 regulates the downstream molecules that promote leukemia invasion into organs. Understanding the molecular interactions helps the researchers to identify new treatment targets. The grant also includes a critical translational component, which is to study the prognostic value of PFKP in detecting the aggressive cases of T-cell acute lymphoblastic leukemia. Additionally, the team will perform preclinical studies of the therapeutic effect of blocking CDK6 in T-cell acute lymphoblastic leukemia animal models.

This funding will help Wang to add research team members to her lab in order to accelerate the studies. "I want to apply the knowledge that we have gained thus far so we can develop a marker to find the more aggressive T-cell malignancy and preclinically test our novel therapeutic strategy to prevent leukemia cellorgan infiltration," Wang said.

The grant funding from NCI began on Aug. 1. This Method to Extend Research in Time (R37) Award is a five-year award with the unique option to extend support for an additional two years.