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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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NEOPLASIA

Brief Report

BCR-ABL1 alters SDF-1{alpha}–mediated adhesive responses through the β2 integrin LFA-1 in leukemia cells

Ying-Yu Chen1, Mobeen Malik2, Brian E. Tomkowicz1, Ronald G. Collman2, and Andrzej Ptasznik1

1 Divisions of Hematology and Oncology and 2 Pulmonary Allergy and Critical Care, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia

Stromal-derived factor-1 (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 β2 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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