title: Distinct microRNA expression profiles in acute myeloid leukemia with common translocations.
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.
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Zejuan
authors.initials: Z
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.forename: Shuangli
authors.initials: S
authors.lastname: Mi
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Roger T
authors.initials: RT
authors.lastname: Luo
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Yungui
authors.initials: Y
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Qian
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Neilly
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
authors.forename: Yanming
authors.initials: Y
authors.lastname: Zhang
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Bohlander
authors.forename: Dong-Er
authors.initials: DE
authors.lastname: Zhang
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Le Beau
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thirman
authors.forename: Todd R
authors.initials: TR
authors.lastname: Golub
authors.forename: Janet D
authors.initials: JD
authors.lastname: Rowley
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D050660:Core Binding Factors / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: D050660:Core Binding Factors; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; C496126:PLK2 protein, human; D017346:Protein Serine-Threonine Kinases