Journal
LEUKEMIA & LYMPHOMA
Volume 43, Issue 1, Pages 19-27Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10428190210188
Keywords
acute lymphoblastic leukemia; stromal cells; apoptosis; chemotherapy; microenvironment
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Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL056888, R29HL056888] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL56888, R01 HL056888] Funding Source: Medline
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Stromal cells are an essential component of the bone marrow microenvironment that regulate development of immature hematopoietic progenitor cells. Through production of soluble cytokines, and signaling through adhesion molecule interactions, stromal cells impact survival, proliferation, and differentiation of hematopoietic progenitor cells. Similarities between normal pro-B and pre-B cells and B lineage acute lymphoblastic leukemic (ALL) progenitors have been well characterized which provide a model for investigation of the mechanisms by which ALL cells respond to bone marrow microenvironment signals. In addition to providing survival signals to B lineage ALL during initiation of disease, the bone marrow has long been recognized as a sanctuary site for leukemic cells during traditional chemotherapy. In the current review, mechanisms by which stromal cells contribute to leukemic cell survival, and the potential impact on treatment efficacy, are discussed. A growing appreciation of the significance of the bone marrow microenvironment in the progression of ALL, and further investigation of the signaling between leukemic progenitors and stromal cells, may contribute to novel treatment strategies aimed at enhancing sensitivity of ALL cells to currently available chemotherapeutic agents.
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