Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Jun;153(6):753-7.
doi: 10.1111/j.1365-2141.2011.08662.x. Epub 2011 Apr 18.

MIR29B regulates expression of MLLT11 (AF1Q), an MLL fusion partner, and low MIR29B expression associates with adverse cytogenetics and poor overall survival in AML

Affiliations

MIR29B regulates expression of MLLT11 (AF1Q), an MLL fusion partner, and low MIR29B expression associates with adverse cytogenetics and poor overall survival in AML

Yin Xiong et al. Br J Haematol. 2011 Jun.

Abstract

MLLT11, an MLL fusion partner, is a poor prognostic biomarker for paediatric acute myeloid leukaemia (AML), adult normal cytogenetics AML, and adult myelodysplastic syndrome. MLLT11 is highly regulated during haematopoietic progenitor differentiation and development but its regulatory mechanisms have not been defined. In this study, we demonstrate by transfection experiments that MIR29B directly regulates MLLT11 expression in vitro. MIR29B expression level was also inversely related to MLLT11 expression in a cohort of 56 AML patients (P<0·05). AML patients with low MIR29B/elevated MLLT11 expression had poor overall survival (P=0·038). Therefore, MIR29B may be a potential prognostic biomarker for AML patients.

PubMed Disclaimer

Figures

Fig 1
Fig 1
Low MIR29B/high MLLT11 expression in AML patient samples and demonstration of direct regulation of MLLT11 by direct interaction of MIR29B with the MLLT11 3-UTR. (A) MLLT11 and MIR29B expression heat map: columns and rows represent patients and MLLT11/MIR29Bexpression, respectively. Red to green indicates high to low expression of MLLT11/MIR29B, respectively. (B) Assessment of expression of MLLT11 mRNA by qRT-PCR and its response to the transfection of miR-29b: transfection of MIR29B into H157 lung cancer cells, SKMES1 lung cancer cells, REH leukaemic cells and a negative control for 24 h, respectively. (C) Assessment of MLLT11 protein level by Western blots in samples corresponding to those of B. (D) GFP reporter stable transfectants in H157 cells showing GFP empty vector (control), GFP-A3U (wild-type), and GFP-A3U-Mutant as well as their images taken by the NIS-Elements image system. Assessment of expression of GFP mRNA by qRT-PCR normalized to neomycin phosphotransferase (NPT) mRNA that also digitally confirmed the image observation. Data in B/C/D are representative of three independent experiments.
Fig 2
Fig 2
Lower MIR29B expression is a poor prognosis marker for AML patients. Kaplan-Meier survival curves for 56 AML patients are stratified by MIR29B expression. AML patients with lower MIR29B expression had a strong trend of adverse cytogenetics (<2·6-fold; P = 0·06) and significantly poorer OS (median OS 1·3-year vs. 2·3-year; P < 0·05) compared to AML patients with higher MIR29B expression (>2·6-fold).

References

    1. Ambros V. microRNAs: tiny regulators with great potential. Cell. 2001;107:823–826. - PubMed
    1. Garzon R, Garofalo M, Martelli MP, Briesewitz R, Wang L, Fernandez-Cymering C, Volinia S, Liu CG, Schnittger S, Haferlach T, Liso A, Diverio D, Mancini M, Meloni G, Foa R, Martelli MF, Mecucci C, Croce CM, Falini B. Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin. Proceedings of the National Academy of Sciences of the United States of America. 2008;105:3945–3950. - PMC - PubMed
    1. Garzon R, Liu S, Fabbri M, Liu Z, Heaphy CE, Callegari E, Schwind S, Pang J, Yu J, Muthusamy N, Havelange V, Volinia S, Blum W, Rush LJ, Perrotti D, Andreeff M, Bloomfield CD, Byrd JC, Chan K, Wu LC, Croce CM, Marcucci G. MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood. 2009;113:6411–6418. - PMC - PubMed
    1. Li Z, Lu J, Sun M, Mi S, Zhang H, Luo RT, Chen P, Wang Y, Yan M, Qian Z, Neilly MB, Jin J, Zhang Y, Bohlander SK, Zhang DE, Larson RA, Le Beau MM, Thirman MJ, Golub TR, Rowley JD, Chen J. Distinct microRNA expressionprofiling in acute myeloid leukemia with common translocation. Proceedings of the National Academy of Sciences of the United States of America. 2008;105:15535–15540. - PMC - PubMed
    1. Li Z, Hassan MQ, Jafferji M, Aqeilan RI, Garzon R, Croce CM, van Wijnen AJ, Stein JL, Stein GS, Lian JB. Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation. Journal of Biological Chemistry. 2009;284:15676–15684. - PMC - PubMed

Publication types

MeSH terms