Learning how leukemia takes over privileged "niches" within the bone marrow is helping researchers develop treatment strategies that could protect healthy blood-forming stem cells and improve the outcomes of bone marrow transplantation for leukemia and other types of cancer.

Hematopoietic progenitor cells (HPCs) home to and engraft in highly specific bone marrow microenvironments, or niches, that regulate their survival, proliferation, and differentiation. Suppression of normal hematopoiesis can occur in the setting of relatively low tumor burden and thus does not necessarily reflect anatomic "crowding out" of benign cells. Although defects in hematopoiesis are frequently observed in patients with malignant involvement of the bone marrow, the molecular bases of these phenomena, and whether they might reflect perturbations in HPC-supportive niches, are unknown.

Researchers at the University of Chicago, led by Dr. Dorothy Sipkins, have shown that leukemic cell growth disrupts normal hematopoietic progenitor cell niches in bone marrow and creates abnormal microenvironments that sequester transplanted human CD34-positive (HPC-enriched) cells. They observed that CD34-positive cells in leukemic mice declined in number over time and failed to mobilize into the peripheral circulation in response to cytokine stimulation. By neutralizing stem cell factor secreted by leukemic cells, Dr. Sipkins group was able to inhibit CD34-positive cell migration into malignant niches, normalize CD34-positive cell numbers, and restore CD34-positive cell mobilization in leukemic mice. These data suggest that inhibition of HPC interaction with tumor niches may help maintain normal progenitor cell function in the setting of malignancy.

File Number: 1706 

Web site: http://biomed.uchicago.edu/common/faculty/sipki...