Distinct microRNA expression profiles in acute myeloid leukemia with common translocations

Zejuan Li, Jun Lu, Miao Sun, Shuangli Mi, Hao Zhang, Roger T. Luo, Ping Chen, Yungui Wang, Ming Yan, Zhijian Qian, Mary Beth Neilly, Jie Jin, Yanming Zhang, Stefan K. Bohlander, Dong Er Zhang, Richard A. Larson, Michelle M. Le Beau, Michael J. Thirman, Todd R. Golub, Janet D. RowleyJianjun Chen

Research output: Contribution to journalArticle

353 Scopus citations

Abstract

MicroRNAs (miRNAs) are postulated to be important regulators in cancers. Here, we report a genome-wide miRNA expression analysis in 52 acute myeloid leukemia (AML) samples with common translocations, including t(8;21)/AML1(RUNX1)-ETO(RUNX1T1), inv(16)/CBFB-MYH11, t(15;17)/PML-RARA, and MLL rearrangements. Distinct miRNA expression patterns were observed for t(15;17), MLL rearrangements, and core-binding factor (CBF) AMLs including both t(8;21) and inv(16) samples. Expression signatures of a minimum of two (i.e., miR-126/126*), three (i.e., miR-224, miR-368, and miR-382), and seven (miR-17-5p and miR-20a, plus the aforementioned five) miRNAs could accurately discriminate CBF, t(15;17), and MLL-rearrangement AMLs, respectively, from each other. We further showed that the elevated expression of miR-126/126* in CBF AMLs was associated with promoter demethylation but not with amplification or mutation of the genomic locus. Our gain- and loss-of-function experiments showed that miR-126/126* inhibited apoptosis and increased the viability of AML cells and enhanced the colony-forming ability of mouse normal bone marrow progenitor cells alone and particularly, in cooperation with AML1-ETO, likely through targeting Polo-like kinase 2 (PLK2), a tumor suppressor. Our results demonstrate that specific alterations in miRNA expression distinguish AMLs with common translocations and imply that the deregulation of specific miRNAs may play a role in the development of leukemia with these associated genetic rearrangements.

Original languageEnglish (US)
Pages (from-to)15535-15540
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number40
DOIs
StatePublished - Oct 7 2008

Keywords

  • Apoptosis and cell viability and proliferation
  • Core binding factor (CBF)
  • MicroRNA expression profiling
  • PLK2
  • miR-126

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Distinct microRNA expression profiles in acute myeloid leukemia with common translocations'. Together they form a unique fingerprint.

  • Cite this

    Li, Z., Lu, J., Sun, M., Mi, S., Zhang, H., Luo, R. T., Chen, P., Wang, Y., Yan, M., Qian, Z., Neilly, M. B., Jin, J., Zhang, Y., Bohlander, S. K., Zhang, D. E., Larson, R. A., Le Beau, M. M., Thirman, M. J., Golub, T. R., ... Chen, J. (2008). Distinct microRNA expression profiles in acute myeloid leukemia with common translocations. Proceedings of the National Academy of Sciences of the United States of America, 105(40), 15535-15540. https://doi.org/10.1073/pnas.0808266105