miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells

Mostrar otras versiones (1)

To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample L...

Descripción completa

Detalles Bibliográficos
Autores principales: Lechman, Eric R., Gentner, Bernhard, Ng, Stanley W.K., Schoof, Erwin M., van Galen, Peter, Kennedy, James A., Nucera, Silvia, Ciceri, Fabio, Kaufmann, Kerstin B., Takayama, Naoya, Dobson, Stephanie M., Trotman-Grant, Aaron, Krivdova, Gabriela, Elzinga, Janneke, Mitchell, Amanda, Nilsson, Björn, Hermans, Karin G., Eppert, Kolja, Marke, Rene, Isserlin, Ruth, Voisin, Veronique, Bader, Gary D., Zandstra, Peter W., Golub, Todd R., Ebert, Benjamin L., Lu, Jun, Minden, Mark, Wang, Jean C.Y., Naldini, Luigi, Dick, John E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749543/
https://www.ncbi.nlm.nih.gov/pubmed/26832662
http://dx.doi.org/10.1016/j.ccell.2015.12.011
Descripción
Sumario:To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Compared with prior results showing miR-126 regulation of normal hematopoietic stem cell (HSC) cycling, these functional stem effects are opposite between LSC and HSC. Combined transcriptome and proteome analysis demonstrates that miR-126 targets the PI3K/AKT/MTOR signaling pathway, preserving LSC quiescence and promoting chemotherapy resistance.

Ejemplares similares