MicroRNA-193b-3p acts as a tumor suppressor by targeting the MYB oncogene in T-cell acute lymphoblastic leukemia

The MYB oncogene is a leucine zipper transcription factor essential for normal and malignant hematopoiesis. In T-cell acute lymphoblastic leukemia (T-ALL), elevated MYB levels can arise directly through T-cell receptor-mediated MYB translocations, genomic MYB duplications or enhanced TAL1 complex bi...

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Bibliographic Details
Published in:Leukemia 2015-04, Vol.29 (4), p.798-806
Main Authors: Mets, E, Van der Meulen, J, Van Peer, G, Boice, M, Mestdagh, P, Van de Walle, I, Lammens, T, Goossens, S, De Moerloose, B, Benoit, Y, Van Roy, N, Clappier, E, Poppe, B, Vandesompele, J, Wendel, H-G, Taghon, T, Rondou, P, Soulier, J, Van Vlierberghe, P, Speleman, F
Format: Article
Language:English
Subjects:
3' Untranslated Regions
Acute lymphoblastic leukemia
Acute lymphocytic leukemia
Animals
Basic Helix-Loop-Helix Transcription Factors - genetics
Basic Helix-Loop-Helix Transcription Factors - metabolism
Care and treatment
Cdc4 protein
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
Development and progression
F-Box Proteins - genetics
F-Box Proteins - metabolism
F-Box-WD Repeat-Containing Protein 7
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Leukemic
Genetic aspects
Genomic Library
Health aspects
Hematopoiesis
Humans
Innovations
Leucine
Leucine zipper proteins
Leukemia
Lymphatic leukemia
Lymphocytes T
Mice
MicroRNA
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
Molecular targeted therapy
Oncogenes
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - metabolism
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology
Primary Cell Culture
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-myb - genetics
Proto-Oncogene Proteins c-myb - metabolism
Ribonucleic acid
RNA
Signal Transduction
T cell receptors
T-Cell Acute Lymphocytic Leukemia Protein 1
T-Lymphocytes - metabolism
T-Lymphocytes - pathology
Transcriptome
Transformations
Translocation
Tumor suppressor genes
Tumors
Ubiquitin-Protein Ligases - genetics
Ubiquitin-Protein Ligases - metabolism
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Summary:The MYB oncogene is a leucine zipper transcription factor essential for normal and malignant hematopoiesis. In T-cell acute lymphoblastic leukemia (T-ALL), elevated MYB levels can arise directly through T-cell receptor-mediated MYB translocations, genomic MYB duplications or enhanced TAL1 complex binding at the MYB locus or indirectly through the TAL1/miR-223/FBXW7 regulatory axis. In this study, we used an unbiased MYB 3'untranslated region-microRNA (miRNA) library screen and identified 33 putative MYB-targeting miRNAs. Subsequently, transcriptome data from two independent T-ALL cohorts and different subsets of normal T-cells were used to select miRNAs with relevance in the context of normal and malignant T-cell transformation. Hereby, miR-193b-3p was identified as a novel bona fide tumor-suppressor miRNA that targets MYB during malignant T-cell transformation thereby offering an entry point for efficient MYB targeting-oriented therapies for human T-ALL.
ISSN:0887-6924
1476-5551
DOI:10.1038/leu.2014.276