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

被引：20

作者：

Chen, Ying-Yu ^{[1
]}

Malik, Mobeen ^{[2
]}

Tomkowicz, Brian E. ^{[1
]}

Collman, Ronald G. ^{[2
]}

Ptasznik, Andrzej ^{[1
]}

机构：

[1] Univ Penn, Sch Med, Dept Med, Div Hematol & Oncol, Philadelphia, PA 19104 USA

[2] Univ Penn, Sch Med, Dept Med, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA

来源：

BLOOD | 2008年 / 111卷 / 10期

关键词：

D O I：

10.1182/blood-2007-10-117705

中图分类号：

R5 [内科学];

学科分类号：

1002 [临床医学]; 100201 [内科学];

摘要：

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 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.

引用

页码：5182 / 5186

页数：5

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