Microenvironmental Regulation of Malignancy

In many hematopoietic malignancies development of cytopenias is a major cause of morbidity and mortality. While the bone marrow microenvironment is essential for the regulation of normal hematopoiesis, little is known about the reliance of leukemic cells on microenvironmental regulation. We have previously used a mouse model of myeloid leukemia to demonstrate a significant loss of osteoblastic cells in the bone marrow. Data from our own lab as well as other subsequent reports suggest that this osteoblastic inhibition is mediated by the chemokine CCL3. These results suggest that leukemic cells alter the microenvironment to improve support for malignancy while decreasing support for normal hematopoiesis. Therefore, our laboratory focuses on the role of CCL3 in leukemic regulation of the microenvironment. We also study the role of the microenvironment as well as strategies to improve support for normal hematopoiesis in myelodysplastic syndromes. To perform this research we utilize mouse models of leukemia as well as primary samples from leukemia patients.

In situ hybridization for Collage 1 mRNA in WT, leukemic day 6, and leukemic day 10 mice.

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