IMAGE: This schematic shows role of RNA splicing in secondary acute myeloid leukemia. view more
Credit: UC San Diego Health
Researchers at University of California San Diego School of Medicine and Moores Cancer Center have identified RNA-based biomarkers that distinguish between normal, aging hematopoietic stem cells and leukemia stem cells associated with secondary acute myeloid leukemia (sAML), a particularly problematic disease that typically afflicts older patients who have often already experienced a bout with cancer.
The findings, published online August 25 in Cell Stem Cell, suggest a new way to predict leukemic relapse early and to identify potential targets for new drug development.
Secondary AML typically follows a chronic pre-malignant disease or treatment for other cancers. Consequently, patients tend to be diagnosed later in life, usually after the age of 60.
“Because of relatively low survival rates and their advancing age, these patients tend to be poor candidates for aggressive therapies, like a bone marrow transplant,” said senior author Catriona Jamieson, MD, PhD, professor of medicine, chief of the Division of Regenerative Medicine at UC San Diego School of Medicine and director of the Stem Cell Research Program at Moores Cancer Center. “There is a pressing need for more effective treatments that prevent disease progression and relapse.”
Aging is a key risk factor for sAML because, over time, hematopoietic stem cells (which give rise to all other blood cell types) accumulate DNA mutations and changes in other molecules that put DNA instructions into action, such as RNA and proteins.
Jamieson’s team wanted to understand how RNA might change with the aging of normal blood stem cells compared with sAML stem cells. “By being able to distinguish benign from malignant aging based on distinctive RNA splicing patterns, we can develop therapeutic strategies that selectively target leukemia …