MicroRNA-193b-3p Acts As a Tumor Suppressor by Targeting the MYB Oncogene in T-cell Acute Lymphoblastic Leukemia

Overview

Journal Leukemia

Specialties Hematology
Oncology

Date 2014 Sep 19

PMID 25231743

Citations 60

Authors

E Mets

J van der Meulen

G Van Peer

M Boice

P Mestdagh

I Van de Walle

T Lammens

S Goossens

B De Moerloose

Y Benoit

N van Roy

E Clappier

B Poppe

J Vandesompele

H-G Wendel

T Taghon

P Rondou

J Soulier

P Van Vlierberghe

F Speleman

Affiliations

Soon will be listed here.

Abstract

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.

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