The National Cancer Institute has awarded Jatinder Lamba, Ph.D., M.Sc., a professor of pharmacotherapy and translational research in the University of Florida College of Pharmacy and a member of the UF Health Cancer Center, a five-year, $1.9 million grant titled, “Genomics of AML Prognosis,” to continue research on Acute Myeloid Leukemia, or AML, that began in 2008.
AML is the second most common childhood leukemia and has a dismal prognosis. For over 40 years, AML chemotherapy has changed little with the continued reliance on three medications for treatment. Lamba’s latest research seeks to incorporate predictable gene expression scores into the risk stratification of AML patients and reveal additional layers of the molecular basis of AML prognosis to guide the development of more effective treatments.
“In previous studies, we have shown that gene scores hold significant value in not only predicting which patients have a high risk of experiencing a relapse, but they help determine which patients can benefit from therapy augmentation or are the best candidates to receive a hematopoietic stem cell transplant,” Lamba said. “Accurate patient classifications can help design better combination therapies and guide future clinical trials involving these transplant therapies.”
Lamba’s current study will evaluate approximately 4,500 patients across 10 national and international cohorts of AML patients treated with intensive chemotherapy. Her other collaborators are Stanley Pounds, Ph.D., a member of the department of biostatistics at St Jude Children’s Research Hospital and Xueyuan Cao, Ph.D., an assistant professor from the University of Tennessee Health Science Center.
The NCI grant continues more than a decade of AML research for Lamba. Her research team initially received funding in 2008 to study the key genes involved in the pathway of cytarabine, the mainstay of chemotherapy in AML patients, and they established the molecular and biological relevance of the genetic variants of these genes. In 2014, NCI funded a study that led to the development of polygenic genomic and transcriptomic scores that predict leukemic cell intracellular levels of drugs and clinical outcomes, among many other accomplishments. This cycle also established the DNA methylation landscape of pediatric AML and identified an enzyme that regulates the methylation landscape as a key predictor of outcome. Since DNA methylation is reversible, these findings have made a significant clinical impact, as they provided the basis for evaluating DNA methylation inhibitors in the ongoing pediatric AML clinical trial (AML16) at St. Jude. In collaboration with Pounds and his team, several machine learning tools have been developed and implemented, which have accelerated present discoveries and increased the potential for its translation into clinics.
In addition to this competing renewal NCI grant award, Lamba also received a two-year grant from the American Cancer Society and St. Baldrick’s Foundation to support the development of Clinical Laboratory Improvement Amendments, or CLIA, certified tests for gene-expression signatures as well as pharmacogenomics markers. The funding will also support further investigation of Children’s Oncology Group clinical trials.