U of M researchers identify genetic variation behind acute myeloid leukemia treatment success

Their study is published today in Clinical Cancer Research.

In the latest study, U of M researchers evaluated how inherited genetic polymorphisms in CD33, a protein that naturally occurs in most leukemia cells, could affect clinical outcomes of patients treated with an existing chemotherapy drug, gemtuzumab ozogamicin (GO), an immuno-conjugate between anti-CD33 antibody and a cytotoxin known as calicheamicin, which binds to CD33 on leukemic cells. As GO is internalized by leukemia cells, the cytotoxin is released, causing DNA damage and generating leukemic cell death.

In recent clinical trials GO has been shown to induce remission and improve survival in subset of patients with AML, however there is wide inter-patient variation in response.

Jatinder Lamba, Ph.D., and colleagues identified and evaluated three genetic variations of CD33 in two groups of patients with pediatric AML – one group that received the drug GO, and one group that did not. They found that specific genetic variation in CD33 that significantly affected the clinical outcome of AML patients who received GO based chemotherapy.

“Understanding how genetics play a role in how drugs work is extremely useful, particularly for a drug like GO which has shown a very heterogeneous response in AML patients,” said Jatinder Lamba, Ph.D., the study's lead author and a researcher who holds appointments in both the College of Pharmacy and the Masonic Cancer Center, University of Minnesota. “Our latest findings lead us to believe that genetic variation in CD33 influences how AML patients' leukemic cell responds to GO.”

AML is a cancer of the blood and bone marrow, and is the second most common form of leukemia in children. Though the most common type of treatment for AML is chemotherapy, Lamba says the disease remains hard to treat and newer, more effective therapies are needed.

“The overall goal of our study was to use genetic data to predict beneficial or adverse response to a specific drug, thus opening up opportunities to use this information for drug optimization to achieve maximum therapeutic efficacy and minimum toxicity. Our hope is that our research could serve as a marker of prognostic significance for clinicians to select the therapy that has the greatest odds of being effective for individual patients based on their CD33 genotype.”

Other University of Minnesota researchers involved in the study include Leslie Mortland, M.D., from the University of Minnesota Medical School and Betsy Hirsch, Ph.D., from the Medical School and the Masonic Cancer Center, University of Minnesota.

The University of Minnesota College of Pharmacy, the only school of pharmacy in Minnesota, offers its program on the Twin Cities and Duluth campuses. Founded in 1892, the College of Pharmacy educates pharmacists and scientists and engages in research and practice to improve the health of the people of Minnesota and society. The college is part of the Academic Health Center, which is home to the University of Minnesota's six health professional schools and colleges as well as several health-related centers and institutes. Learn more at www.pharmacy.umn.edu.

The University of Minnesota Medical School, with its two campuses in the Twin Cities and Duluth, is a leading educator of the next generation of physicians. Our graduates and the school's 3,800 faculty physicians and scientists advance patient care, discover biomedical research breakthroughs with more than $180 million in sponsored research annually, and enhance health through world-class patient care for the state of Minnesota and beyond. Visit www.med.umn.edu to learn more.

Masonic Cancer Center, University of Minnesota is part of the University's Academic Health Center. It is designated by the National Cancer Institute as a Comprehensive Cancer Center. For more information about the Masonic Cancer Center, visit www.cancer.umn.edu or call 612-624-2620.