PMID: 9178724Jun 1, 1997Paper

Pathophysiology of CML: do defects in integrin function contribute to the premature circulation and massive expansion of the BCR/ABL positive clone?

The Journal of Laboratory and Clinical Medicine
C M VerfaillieR Bhatia

Abstract

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 beta1-integrin receptors to fibronectin not only anchor progenitors to the stroma but also result in direct adhesion-mediated signaling that inhibits progenitor proliferation. In contrast to normal hematopoiesis, chronic myelogenous leukemia (CML) is characterized not only by abnormal, premature circulation of primitive progenitors in the blood but also by continuous progenitor proliferation. Although CML progenitors express the same integrin receptors as normal progenitors, they fail to adhere to stroma and fibronectin, suggesting structural or functional abnormalities of these receptors. Furthermore, CML cells present in contact with stroma or fibronectin continue to proliferate, suggesting that failure to adhere through integrin receptors may also underlie the abnormal proliferation of CML progenitors. The observation that integrin-mediated adhesion and proliferation-inhibitory signaling can be restored through treatment with interferon-alpha or an activating anti-beta1-integrin antibody suggests a functiona...Continue Reading

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Citations

May 30, 2001·Experimental Hematology·B N JahagirdarC M Verfaillie
Jul 15, 1999·The New England Journal of Medicine·S FaderlH M Kantarjian
Oct 19, 2010·Carcinogenesis·Adriana BorrielloFulvio Della Ragione
Apr 3, 2012·Journal of Molecular Cell Biology·Alexandre PuissantPatrick Auberger
Aug 27, 2005·Clinical Pharmacokinetics·Bin PengHorst Schran
Jul 21, 2011·Journal of Cell Communication and Signaling·Lynn McCallumAlexandra E Irvine
Feb 13, 2007·Seminars in Hematology·Ricardo H AlvarezJorge E Cortes
Mar 22, 2001·Hematology/oncology Clinics of North America·J P Radich
Jul 24, 2004·Hematology/oncology Clinics of North America·Junia V Melo, Michael W N Deininger
Dec 12, 2002·Oncogene·Jason A WertheimWarren S Pear
Jun 22, 2005·Clinical Science·Stephen B Marley, Myrtle Y Gordon
May 11, 2006·Archives of Pathology & Laboratory Medicine·Mark R Litzow

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