Submitted October 10, 2007
Accepted March 8, 2008
BCR-ABL1 alters SDF-1
mediated adhesive responses through the 
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 
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.
