BCR-ABL1 alters SDF-1α-mediated adhesive responses through the β2 integrin LFA-1 in leukemia cells

Abstract

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. © 2008 by The American Society of Hematology.