MEIS1-mediated transactivation of synaptotagmin-like 1 promotes CXCL12/CXCR4 signaling and leukemogenesis
- Yokoyama, T., Nakatake, M., Kuwata, T., Couzinet, A., Goitsuka, R., Tsutsumi, S., Aburatani, H., Valk, P.J.M., Delwel, R., Nakamura, T.
- J. Clin, Invest., 2016, in press, doi:10.1172/JCI81516
Meis1 is a TALE-class homeodomain transcription factor that is important in hematopoiesis, vasculogenesis, cardiac development and eye development. Meis1 is also important for Hox functions in myeloid leukemogenesis. However, its functions in leukemogenesis and the significance of its cooperation with Hox have not been clarified. In this manuscript, we focus on an important issue in leukemia biology regarding the identity of pathologically relevant target genes for Meis1. We demonstrated that Meis1’s function is important in leukemogenesis through its impact on leukemic cell homing, engraftment, cell-cell interaction and migration. We identified Sytl1 as a direct transcriptional target for Meis1, and Sytl1 does indeed cooperate with Hoxa9. Sytl1 facilitates membrane trafficking of CXCR4, thus enhancing cell migration and engraftment. These results such as 1) Meis1 functions in leukemic cell homing and engraftment, 2) direct regulation of Sytl1 by Meis1, 3) SYTL1 expression in human AML, 4) Sytl1 function in migration and motility of leukemic cells and 5) membrane trafficking of CXCR4 by Sytl1 are quite novel and uncover the function of Meis1 in leukemia.