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

Shiozawa, Yusuke; Pedersen, Elisabeth A.; Taichman, Russell S.

doi:10.1016/j.exphem.2009.11.002

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Volume 38, Issue 2 , Pages 132-140, February 2010

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

Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Mich., USA

Received 4 August 2009; received in revised form 3 November 2009; accepted 9 November 2009. published online 16 November 2009.

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.