Interaction of acute leukemia cells with the bone marrow microenvironment: implications for control of minimal residual disease
Abstract
There is increasing evidence for an interaction between acute leukemia cells and the microenvironment of the bone marrow. Blast cells from cases of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) bind to cellular and extracellular matrix components of the bone marrow stroma. In AML, adhesion to stroma is mediated by the combined action of beta 1 (principally VLA-4) and beta 2 integrins, while in precursor-B ALL VLA-4 and VLA-5 integrins play a major role. Adhesion molecules such as CD31, CD44, non-beta 1, beta 2 integrins, growth factor receptors such as c-kit, and other molecules are also likely to play a role. Binding of acute leukemia blasts to ligands on stroma has several pathophysiological consequences. Stromal contact is able to inhibit programmed cell death (apoptosis) in a proportion of cases of both AML and ALL. In ALL, diffusible molecules derived from stroma appear to contribute. Marrow stroma also plays a part in regulating leukemic cell proliferation. While this is partly due to stromal production of hemopoietic growth factors, in soluble or transmembrane form or bound to extracellular matrix, signalling mediated directly by binding of adhesion molecules on leukemic cells may also have a role. ...Continue Reading
References
Role of beta 1 and beta 2 integrins in the adhesion of human CD34hi stem cells to bone marrow stroma
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