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

Summary, in English

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.

• Author: Eric R Lechman; Bernhard Gentner; Stanley W K Ng; Erwin M Schoof; Peter van Galen; James A Kennedy; Silvia Nucera; Fabio Ciceri; Kerstin B Kaufmann; Naoya Takayama; Stephanie M Dobson; Aaron Trotman-Grant; Gabriela Krivdova; Janneke Elzinga; Amanda Mitchell; Björn Nilsson; Karin G Hermans; Kolja Eppert; Rene Marke; Ruth Isserlin; Veronique Voisin; Gary D Bader; Peter W Zandstra; Todd R Golub; Benjamin L Ebert; Jun Lu; Mark Minden; Jean C Y Wang; Luigi Naldini; John E Dick
• Department/s: Division of Hematology and Transfusion Medicine; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
• Publishing year: 2016
• Language: English
• Pages: 214-228
• Publication/Series: Cancer Cell
• Volume: 29
• Issue: 2
• Links: http://www.ncbi.nlm.nih.gov/pubmed/26832662?dopt=Abstract; http://dx.doi.org/10.1016/j.ccell.2015.12.011
• Document type: Journal article
• Publisher: Cell Press
• Topic: Cancer and Oncology
• Status: Published
• ISBN/ISSN/Other: ISSN: 1878-3686