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 Blood, 15 May 2008, Vol. 111, No. 10, pp. 5182-5186.
Prepublished online as a Blood First Edition Paper on March 13, 2008; DOI 10.1182/blood-2007-10-117705.

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Submitted October 10, 2007
Accepted March 8, 2008

BCR-ABL1 alters SDF-1{alpha} mediated adhesive responses through the {beta}2 integrin LFA-1 in leukemia cells

Ying-Yu Chen, Mobeen Malik, Brian E. Tomkowicz, Ronald G. Collman, and Andrzej Ptasznik*

Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, United States
Division of Pulmonary Allergy & Critical Care, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, United States

* Corresponding author; email: andrzejp{at}mail.med.upenn.edu.

Stromal-derived factor (SDF)-1 and its receptor, CXCR4, are essential for normal hematopoietic progenitor cell movement and adherence within the bone marrow microenvironment. In leukemia, the BCR-ABL1 oncoprotein inhibits SDF-1-dependent cell trafficking within the bone marrow through a mechanism that is not fully understood. Here we report that BCR-ABL1 in malignant cells constitutively increases expression of activation-dependent epitopes of the {beta}2 integrin LFA-1. This is associated with the complete loss of responsiveness of LFA-1 to SDF-1-induced "inside-out" signaling involving CXCR4 and Lyn, leading to aberrant adhesive responses. These data provide a novel, LFA-1-mediated mechanism, whereby BCR-ABL1 inhibits SDF-1 action in malignant progenitors.


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This article has been cited by other articles:


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M. Malik, Y.-Y. Chen, M. F. Kienzle, B. E. Tomkowicz, R. G. Collman, and A. Ptasznik
Monocyte Migration and LFA-1-Mediated Attachment to Brain Microvascular Endothelia Is Regulated by SDF-1{alpha} through Lyn Kinase
J. Immunol., October 1, 2008; 181(7): 4632 - 4637.
[Abstract] [Full Text] [PDF]


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