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Medline ® Abstract for Reference 163

of '慢性髓系白血病的细胞和分子生物学'

Integrin-mediated regulation of hematopoiesis: do BCR/ABL-induced defects in integrin function underlie the abnormal circulation and proliferation of CML progenitors?
Verfaillie CM, Hurley R, Lundell BI, Zhao C, Bhatia R
Acta Haematol. 1997;97(1-2):40.
Hematopoiesis takes place in close contact with the marrow microenvironment. Normal progenitors adhere through a variety of receptors to stroma and extracellular matrix components, including fibronectin. Adhesion through integrins to fibronectin may not only serve to anchor progenitors to the microenvironment but also to directly alter the proliferative behavior of normal hematopoietic progenitors. Chronic myelogenous leukemia (CML) is a malignant disease of the hematopoietic stem cell. At the molecular level, CML is characterized by the BCR/ABL gene rearrangement which encodes for the oncoprotein, p210bcr-abl. Presence of the p210bcr-abl tyrosine kinase is necessary and sufficient for the malignant transformation of hematopoietic cells. Clinically, CML is characterized by an abnormal, premature release of primitive progenitors and precursors in the blood and by the continuous proliferation of the malignant progenitor population. In vitro, CML progenitors fail to adhere to or be regulated by marrow stroma. Since CML progenitors express similar numbers of integrin adhesion receptors as normal progenitors, functional rather than quantitative differences of these receptors on CML progenitors may be responsible for the abnormal circulation and proliferation of the malignant clone. In this manuscript we will review the role of integrin adhesion receptors present on normal hematopoietic progenitors in the regulation of their proliferation and discuss signal transduction mechanisms that may be responsible for these effects. We will also discuss the integrin defect in CML which may be caused by the presence of the oncoprotein, P210bcr-abl, and may explain the abnormal trafficking and proliferation observed in CML.
Department of Medicine, University of Minnesota, Minneapolis 55455, USA.