New research shows search and destroy function for leukemia cells

kurre-_pape-brochure-pic-2014The rapid growth of leukemia cells that “crowd out” healthy stem cells within the bone marrow has traditionally been considered the root cause for prolonged risk of infections and necessary blood transfusions. A study recently completed by a team of OHSU pediatric cancer biology researchers in the Pape Family Pediatric Research Institute – and published in the journal Science Signaling –  disputes this theory and provides the first description of leukemia cells’ ability to actively target and destroy healthy cells in bone marrow throughout the body. The identification of this process creates an opportunity for the development of new, targeted therapies to protect cells and potentially limit prolonged hospital and clinic admissions for leukemia patients.

Led by principal investigator Peter Kurre, M.D., the team discovered this process by identifying small vesicles, or exosomes, released from acute myeloid leukemia cells and their systematic study in mouse models. The leukemia vesicles circulate in the bloodstream and serve as messengers of small regulatory molecules, or microRNA. The research team showed that these vesicles act by degrading the machinery central to the function of healthy bone marrow stem cells and are unaffected by traditional cancer therapies.

Along with other studies in the field, this discovery suggests the effect of cancer may not be locally limited, but instead has the capacity to compromise healthy tissue function even before the spread of cancer cells.

 The paper, “AML suppresses hematopoiesis by releasing exosomes that contain microRNAs targeting c-MYB,” was supported in part by a grant from Hyundai Hope on Wheels. The research team included Kurre and members of his lab–Noah I. Hornick (co-first author), Ben Doron (co-first author), Sherif Abdelhamed, Kianya Huan, and Santhosh Chakkaramakkil Verghese–as well as OHSU faculty members  Christina A. Harrington and  Xiaolu A. Cambronne; and Rongkun Shen, from the College at Brockport, State University of New York.