It is well understood that people with diabetes have an increased risk for a number of other health complications—including cancer. Last year, when Indiana University School of Medicine researchers demonstrated that inflammation can increase risk for leukemia, they wondered if it was also the culprit that placed people with diabetes at a higher risk for blood cancer. Now, a large research grant will help them find answers.
Reuben Kapur, PhD, has been awarded $2.3 million from the National Heart, Lung and Blood Institute to study the progression of preleukemic stem cells—those bearing certain mutations associated with leukemia—to full-blown cancer in the context of diabetes. They will use the funds to examine and assess cancer progression under conditions of hyperglycemia, or high blood sugar, in animal models over the next four years.
“Insulin regulates blood sugar levels, so people with diabetes—whose bodies don’t make a sufficient amount of insulin—can easily become hyperglycemic,” said Raghu Mirmira, MD, PhD, diabetes researcher and collaborator for the study. “Over time, hyperglycemia can cause damage to cells and tissues, putting people with diabetes at higher risk for developing other health issues.”
Kapur said that his team hypothesizes that hyperglycemia in blood stem cells and progenitor cells can destabilize the expression of tumor suppression genes, which prevent cancer development.
“When expression of tumor suppressors is lost or destabilized, cells grow uncontrollably and can eventually lead to cancer,” said Kapur. “Our early data suggest that a tumor suppressor called TET2 gets destabilized when exposed to high glucose.”
A 2018 study from Kapur and his colleagues at the IU Simon Cancer Center and the Herman B Wells Center for Pediatric Research showed that inflammation contributes to the proliferation of preleukemic cells that have the TET2 mutation, thereby increasing the risk for leukemia. They also identified drug molecules—developed by the laboratory of Mark Kelley, PhD, and Apexian Pharmaceuticals—that block the pathways that cause the spread of the preleukemic cells.
They wondered if certain conditions that cause chronic inflammation, such as diabetes, could have the same effect on the mutated cells. And if so, will the same drugs help to reduce risk?
The project referenced above is titled Hyperglycemia Mediatated Myeloprolaferitive Disease, project number 1R01HL140961-01A1. Funds have been awarded by the National Heart, Lung, and Blood Institute.
Reuben Kapur, PhD, is the Frieda and Albrecht Kipp Professor of Pediatrics, director of the Hematologic Malignancies and Stem Cell Biology research program at the Herman B Wells Wells Center for Pediatric Research and co-director of the Hematopoiesis, Hematologic Malignancies and Immunology research program at the IU Simon Cancer Center.
Raghu Mirmira, MD, PhD, is the Eli Lilly and Company Professor of Pediatric Diabetes. He is the director of the Center for Diabetes and Metabolic Diseases, the Herman B Wells Center for Pediatric Disease, and the NIH-funded Medical Scientist Training Program at Indiana University School of Medicine.