Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109-1078, USA.
Exp Hematol. 2010 Feb;38(2):132-40. doi: 10.1016/j.exphem.2009.11.002. Epub 2009 Nov 14.
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.
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.
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.
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.
尽管目前联合化疗方案有所改进，但（1；19）（q23;p13）易位（E2A/PBX1）阳性 B 细胞前体急性淋巴细胞白血病（ALL）患儿的预后仍较差。
在本研究中，我们研究了生长停滞特异性基因-6（GAS6）/Mer 轴在 E2A/PBX1 阳性 B 细胞前体 ALL 细胞与骨髓成骨细胞龛之间相互作用中的作用。
数据表明，原代人成骨细胞通过丝裂原活化蛋白激酶信号通路对 Mer 过表达的 E2A/PBX1 阳性 ALL 细胞分泌 GAS6，白血病细胞通过 Mer 激活的途径向 GAS6 迁移。重要的是，GAS6 通过诱导休眠来支持 E2A/PBX1 阳性 ALL 细胞的存活并防止化疗引起的细胞凋亡。
这些数据表明，GAS6/Mer 轴调节 E2A/PBX1 阳性 B 细胞前体 ALL 在骨髓龛中的归巢和存活。
