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Proc Natl Acad Sci U S A DOI:10.1073/pnas.0808266105

Distinct microRNA expression profiles in acute myeloid leukemia with common translocations.

Publication TypeJournal Article
Year of Publication2008
AuthorsLi, Z, Lu, J, Sun, M, Mi, S, Zhang, H, Luo, RT, Chen, P, Wang, Y, Yan, M, Qian, Z, Neilly, MBeth, Jin, J, Zhang, Y, Bohlander, SK, Zhang, D-E, Larson, RA, Le Beau, MM, Thirman, MJ, Golub, TR, Rowley, JD, Chen, J
JournalProc Natl Acad Sci U S A
Volume105
Issue40
Pages15535-40
Date Published2008 Oct 07
ISSN1091-6490
KeywordsAnimals, Apoptosis, Cell Survival, Core Binding Factors, Gene Expression Profiling, Humans, Leukemia, Myeloid, Acute, Mice, MicroRNAs, Mutation, Protein-Serine-Threonine Kinases, Translocation, Genetic
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.

URLhttp://www.pnas.org/cgi/pmidlookup?view=long&pmid=18832181
DOI10.1073/pnas.0808266105
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/18832181?dopt=Abstract

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID18832181
PubMed Central IDPMC2563085
Grant ListCA40046 / CA / NCI NIH HHS / United States
P01 CA040046 / CA / NCI NIH HHS / United States
CA127277 / CA / NCI NIH HHS / United States
P30 CA014599 / CA / NCI NIH HHS / United States
R01 CA104509 / CA / NCI NIH HHS / United States
CA104509 / CA / NCI NIH HHS / United States
R01 CA127277 / CA / NCI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
CA014599 / CA / NCI NIH HHS / United States