CD49d/Integrin alpha 4
Integrin alpha-4 (CD49d) assembles into two immunologically distinct receptors: alpha4 beta1 (VLA-4), which binds VCAM-1 and the CS-1 region of fibronectin, and alpha4 beta7, the gut-homing receptor for MAdCAM-1. VLA-4 differs from most integrins in mediating leukocyte adhesion without dependence on prior selectin rolling, and it anchors hematopoietic progenitors and chronic lymphocytic leukemia cells in protective marrow niches. This biology made CD49d a flagship drug target: natalizumab blocks both alpha4 heterodimers in multiple sclerosis and Crohn disease, vedolizumab selectively inhibits alpha4 beta7, and anti-VLA-4 agents that disrupt leukemia-stroma interactions are under clinical study. Flow cytometric quantification of CD49d stratifies CLL prognosis.
