GAS6/Mer axis regulates the homing and survival of the E2A/PBX1-positive B-cell precursor acute lymphoblastic leukemia in the bone marrow niche

Objective. Despite improvements in current combinational chemotherapy regimens, the prognosis of the (1;19)(q23;p13) translocation (E2A/PBX1)-positive B-cell precursor acute lymphoblastic leukemia (ALL) is poor in pediatric leukemia patients. Materials and Methods. In this study, we examined the roles of growth arrest-specific-6 (GAS6)/Mer axis in the interactions between E2A/PBX1-positive B-cell precursor ALL cells and the osteoblastic niche in the bone marrow. Results. Data show that primary human osteoblasts secrete GAS6 in response to the Mer-overexpressed E2A/PBX1-positive ALL cells through mitogen-activated protein kinase signaling pathway and that leukemia cells migrate toward GAS6 using pathways activated by Mer. Importantly, GAS6 supports survival and prevents apoptosis from chemotherapy of E2A/PBX1-positive ALL cells by inducing dormancy. Conclusions. These data suggest that GAS6/Mer axis regulates homing and survival of the E2A/PBX1-positive B-cell precursor ALL in the bone marrow niche. (C) 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.