Multiple myeloma and integrins

Abstract

Integrins play an important role in the homing, survival, proliferation, and drug resistance of multiple myeloma (MM) cells in the bone marrow. Among the many integrin families, the integrins α4β1 (VLA-4) and α4β7 have been reported to have important functions in MM cells. Previous studies have also reported that the three-dimensional structure of an integrin changes depending on its activation state; however, the conformations of integrins expressed in MM cells have not been studied so far. We recently observed that integrin α4β7 constitutively adopts an active conformation in MM cells, and chimeric antigen receptor (CAR) T cell therapy that targets the activated conformation of integrin β7 is a promising new treatment for MM. We are now clarifying the mechanism for the constitutive activation of integrin β7 in MM and its relationship with the pathology of MM.