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.


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.
Shiozawa
Yusuke
Y
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109-1078, USA.
Pedersen
Elisabeth A
EA
Taichman
Russell S
RS
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis*; D001853:Bone Marrow / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002633:Chemotaxis; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D004268:DNA-Binding Proteins / Q000032:analysis*; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D010006:Osteoblasts / Q000378:metabolism; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D000076202:c-Mer Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
D000970:Antineoplastic Agents; D051792:Basic Helix-Loop-Helix Proteins; D017077:Culture Media, Conditioned; D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C407909:TCF3 protein, human; C083400:PBX1 protein, human; C097072:MERTK protein, human