A cooperative microRNA-tumor suppressor gene network in acute T-cell lymphoblastic leukemia (T-ALL) Journal Article


Authors: Mavrakis, K. J.; Van Der Meulen, J.; Wolfe, A. L.; Liu, X.; Mets, E.; Taghon, T.; Khan, A. A.; Setty, M.; Rondou, P.; Vandenberghe, P.; Delabesse, E.; Benoit, Y.; Socci, N.; Leslie, C. S.; Van Vlierberghe, P.; Speleman, F.; Wendel, H. G.
Article Title: A cooperative microRNA-tumor suppressor gene network in acute T-cell lymphoblastic leukemia (T-ALL)
Abstract: The importance of individual microRNAs (miRNAs) has been established in specific cancers. However, a comprehensive analysis of the contribution of miRNAs to the pathogenesis of any specific cancer is lacking. Here we show that in T-cell acute lymphoblastic leukemia (T-ALL), a small set of miRNAs is responsible for the cooperative suppression of several tumor suppressor genes. Cross-comparison of miRNA expression profiles in human T-ALL with the results of an unbiased miRNA library screen allowed us to identify five miRNAs (miR-19b, miR-20a, miR-26a, miR-92 and miR-223) that are capable of promoting T-ALL development in a mouse model and which account for the majority of miRNA expression in human T-ALL. Moreover, these miRNAs produce overlapping and cooperative effects on tumor suppressor genes implicated in the pathogenesis of T-ALL, including IKAROS (also known as IKZF1), PTEN, BIM, PHF6, NF1 and FBXW7. Thus, a comprehensive and unbiased analysis of miRNA action in T-ALL reveals a striking pattern of miRNA-tumor suppressor gene interactions in this cancer. © 2011 Nature America, Inc. All rights reserved.
Keywords: controlled study; protein expression; nonhuman; conference paper; mouse; animal tissue; microrna; embryo; animal experiment; animal model; tumor suppressor gene; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; t cell leukemia; cooperation; ikaros transcription factor; hepatocyte nuclear factor 1
Journal Title: Nature Genetics
Volume: 43
Issue: 7
ISSN: 1061-4036
Publisher: Nature Publishing Group  
Date Published: 2011-07-01
Start Page: 673
End Page: 678
Language: English
DOI: 10.1038/ng.858
PROVIDER: scopus
PUBMED: 21642990
PMCID: PMC4121855
DOI/URL:
Notes: --- - "Export Date: 17 August 2011" - "CODEN: NGENE" - "Source: Scopus"
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MSK Authors
  1. Nicholas D Socci
    202 Socci
  2. Hans Guido Wendel
    72 Wendel
  3. Christina Leslie
    131 Leslie
  4. Manu Setty
    26 Setty
  5. Andrew Lerner Wolfe
    11 Wolfe
  6. Aly Azeem Khan
    8 Khan
  7. Xiaoping Liu
    6 Liu