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

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Standard

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

I: Cancer Cell, Bind 29, Nr. 2, 08.02.2016, s. 214-228.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Lechman, ER, Gentner, B, Ng, SWK, Schoof, EM, van Galen, P, Kennedy, JA, Nucera, S, Ciceri, F, Kaufmann, KB, Takayama, N, Dobson, SM, Trotman-Grant, A, Krivdova, G, Elzinga, J, Mitchell, A, Nilsson, B, Hermans, KG, Eppert, K, Marke, R, Isserlin, R, Voisin, V, Bader, GD, Zandstra, PW, Golub, TR, Ebert, BL, Lu, J, Minden, M, Wang, JCY, Naldini, L & Dick, JE 2016, 'MiR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells', Cancer Cell, bind 29, nr. 2, s. 214-228. https://doi.org/10.1016/j.ccell.2015.12.011

APA

Lechman, E. R., Gentner, B., Ng, S. W. K., Schoof, E. M., van Galen, P., Kennedy, J. A., Nucera, S., Ciceri, F., Kaufmann, K. B., Takayama, N., Dobson, S. M., Trotman-Grant, A., Krivdova, G., Elzinga, J., Mitchell, A., Nilsson, B., Hermans, K. G., Eppert, K., Marke, R., ... Dick, J. E. (2016). MiR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells. Cancer Cell, 29(2), 214-228. https://doi.org/10.1016/j.ccell.2015.12.011

Vancouver

Lechman ER, Gentner B, Ng SWK, Schoof EM, van Galen P, Kennedy JA o.a. MiR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells. Cancer Cell. 2016 feb. 8;29(2):214-228. https://doi.org/10.1016/j.ccell.2015.12.011

Author

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. / MiR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells. I: Cancer Cell. 2016 ; Bind 29, Nr. 2. s. 214-228.

Bibtex

@article{541bb6b354e5409884d3dcb8a714b156,
title = "MiR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells",
abstract = "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. Lechman et al. show that miR-126 targets the PI3K/AKT/MTOR signaling pathway to preserve quiescence, increase self-renewal, and promote chemotherapy resistance of acute myeloid leukemia stem cells (LSC). Reducing the miR-126 level impairs LSC maintenance in contrast to expanding normal hematopoietic stem cells.",
author = "Lechman, {Eric R.} and Bernhard Gentner and Ng, {Stanley W.K.} and Schoof, {Erwin M.} and {van Galen}, Peter and Kennedy, {James A.} and Silvia Nucera and Fabio Ciceri and Kaufmann, {Kerstin B.} and Naoya Takayama and Dobson, {Stephanie M.} and Aaron Trotman-Grant and Gabriela Krivdova and Janneke Elzinga and Amanda Mitchell and Bj{\"o}rn Nilsson and Hermans, {Karin G.} and Kolja Eppert and Rene Marke and Ruth Isserlin and Veronique Voisin and Bader, {Gary D.} and Zandstra, {Peter W.} and Golub, {Todd R.} and Ebert, {Benjamin L.} and Jun Lu and Mark Minden and Wang, {Jean C.Y.} and Luigi Naldini and Dick, {John E.}",
note = "Funding Information: We thank Dr. M Roehrl for mass spectrometer support, A Khandani and P. A. Penttil{\"a} for flow cytometry, and the Dick and Naldini laboratories for critical review. This work was supported by grants to L.N. from Telethon (TIGET grant), EU ( FP7 GA 222878 PERSIST, ERC Advanced Grant 249845 TARGETING GENE THERAPY), and the Italian Ministry of Health and to J.E.D. from the Canadian Institutes for Health Research , Canadian Cancer Society , Terry Fox Foundation , Genome Canada through the Ontario Genomics Institute , Ontario Institute for Cancer Research with funds from the Province of Ontario , and a Canada Research Chair . E.M.S. is an EMBO Postdoctoral Fellow (ALTF 1595–2014) and is co-funded by the European Commission (LTFCOFUND2013, GA-2013-609409 ) and Marie Curie Actions . This research was funded in part by the Ontario Ministry of Health and Long Term Care (OMOHLTC). The views expressed do not necessarily reflect those of the OMOHLTC. Publisher Copyright: {\textcopyright} 2016 The Authors.",
year = "2016",
month = feb,
day = "8",
doi = "10.1016/j.ccell.2015.12.011",
language = "English",
volume = "29",
pages = "214--228",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",

}

RIS

TY - JOUR

T1 - MiR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells

AU - Lechman, Eric R.

AU - Gentner, Bernhard

AU - Ng, Stanley W.K.

AU - Schoof, Erwin M.

AU - van Galen, Peter

AU - Kennedy, James A.

AU - Nucera, Silvia

AU - Ciceri, Fabio

AU - Kaufmann, Kerstin B.

AU - Takayama, Naoya

AU - Dobson, Stephanie M.

AU - Trotman-Grant, Aaron

AU - Krivdova, Gabriela

AU - Elzinga, Janneke

AU - Mitchell, Amanda

AU - Nilsson, Björn

AU - Hermans, Karin G.

AU - Eppert, Kolja

AU - Marke, Rene

AU - Isserlin, Ruth

AU - Voisin, Veronique

AU - Bader, Gary D.

AU - Zandstra, Peter W.

AU - Golub, Todd R.

AU - Ebert, Benjamin L.

AU - Lu, Jun

AU - Minden, Mark

AU - Wang, Jean C.Y.

AU - Naldini, Luigi

AU - Dick, John E.

N1 - Funding Information: We thank Dr. M Roehrl for mass spectrometer support, A Khandani and P. A. Penttilä for flow cytometry, and the Dick and Naldini laboratories for critical review. This work was supported by grants to L.N. from Telethon (TIGET grant), EU ( FP7 GA 222878 PERSIST, ERC Advanced Grant 249845 TARGETING GENE THERAPY), and the Italian Ministry of Health and to J.E.D. from the Canadian Institutes for Health Research , Canadian Cancer Society , Terry Fox Foundation , Genome Canada through the Ontario Genomics Institute , Ontario Institute for Cancer Research with funds from the Province of Ontario , and a Canada Research Chair . E.M.S. is an EMBO Postdoctoral Fellow (ALTF 1595–2014) and is co-funded by the European Commission (LTFCOFUND2013, GA-2013-609409 ) and Marie Curie Actions . This research was funded in part by the Ontario Ministry of Health and Long Term Care (OMOHLTC). The views expressed do not necessarily reflect those of the OMOHLTC. Publisher Copyright: © 2016 The Authors.

PY - 2016/2/8

Y1 - 2016/2/8

N2 - 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. Lechman et al. show that miR-126 targets the PI3K/AKT/MTOR signaling pathway to preserve quiescence, increase self-renewal, and promote chemotherapy resistance of acute myeloid leukemia stem cells (LSC). Reducing the miR-126 level impairs LSC maintenance in contrast to expanding normal hematopoietic stem cells.

AB - 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. Lechman et al. show that miR-126 targets the PI3K/AKT/MTOR signaling pathway to preserve quiescence, increase self-renewal, and promote chemotherapy resistance of acute myeloid leukemia stem cells (LSC). Reducing the miR-126 level impairs LSC maintenance in contrast to expanding normal hematopoietic stem cells.

UR - http://www.scopus.com/inward/record.url?scp=84958635003&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2015.12.011

DO - 10.1016/j.ccell.2015.12.011

M3 - Journal article

C2 - 26832662

AN - SCOPUS:84958635003

VL - 29

SP - 214

EP - 228

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 2

ER -

ID: 359859655