Rac-1 GTPase controls the capacity of human leukaemic lymphoblasts to migrate on fibronectin in response to SDF-1α (CXCL12)

Acute lymphoblastic leukaemia (ALL) is characterized by malignant cell infiltration of bone marrow, requiring chemotactic response to SDF-1 alpha. Using time-lapse video, we measured the velocity of ALL cells on fibronectin, and found that SDF-1 alpha increased their migration activity for 2 h, but had no effect after 4 h, following internalization of its receptor CXCR4. Transfection of ALL cells with dominant-negative Rac1 mutant significantly prolonged their chemotactic response to SDF-1 alpha, and this effect was associated with an alteration of CXCR4 internalization. These data suggest a regulatory role for Rac1 in the chemotactic response of ALL cells to SDF-1 alpha via receptor processing. (C) 2011 Elsevier Ltd. All rights reserved.