title: Clinical role of microRNAs in cytogenetically normal acute myeloid leukemia: miR-155 upregulation independently identifies high-risk patients.
abstract: OBJECTIVE
  To evaluate the impact of miR-155 on the outcome of adults with cytogenetically normal (CN) acute myeloid leukemia (AML) in the context of other clinical and molecular prognosticators and to gain insight into the leukemogenic role of this microRNA.
  
  
  METHODS
  We evaluated 363 patients with primary CN-AML. miR-155 levels were measured in pretreatment marrow and blood by NanoString nCounter assays that quantified the expression of the encoding gene MIR155HG. All molecular prognosticators were assessed centrally. miR-155-associated gene and microRNA expression profiles were derived using microarrays.
  
  
  RESULTS
  Considering all patients, high miR-155 expression was associated with a lower complete remission (CR) rate (P < .001) and shorter disease-free survival (P = .001) and overall survival (OS; P < .001) after adjusting for age. In multivariable analyses, high miR-155 expression remained an independent predictor for a lower CR rate (P = .007) and shorter OS (P < .001). High miR-155 expressers had approximately 50% reduction in the odds of achieving CR and 60% increase in the risk of death compared with low miR-155 expressers. Although high miR-155 expression was not associated with a distinct microRNA expression profile, it was associated with a gene expression profile enriched for genes involved in cellular mechanisms deregulated in AML (eg, apoptosis, nuclear factor-κB activation, and inflammation), thereby supporting a pivotal and unique role of this microRNA in myeloid leukemogenesis.
  
  
  CONCLUSIONS
  miR-155 expression levels are associated with clinical outcome independently of other strong clinical and molecular predictors. The availability of emerging compounds with antagonistic activity to microRNAs in the clinic provides the opportunity for future therapeutic targeting of miR-155 in AML.
authors: The Ohio State University, Comprehensive Cancer Center, Biomedical Research Tower 460 W. 12th Ave, Columbus, OH 43210, USA. guido.marcucci@osumc.edu
authors: Guido
authors: G
authors: Marcucci
authors: Kati S
authors: KS
authors: Maharry
authors: Klaus H
authors: KH
authors: Metzeler
authors: Stefano
authors: S
authors: Volinia
authors: Yue-Zhong
authors: YZ
authors: Wu
authors: Krzysztof
authors: K
authors: Mrózek
authors: Deedra
authors: D
authors: Nicolet
authors: Jessica
authors: J
authors: Kohlschmidt
authors: Susan P
authors: SP
authors: Whitman
authors: Jason H
authors: JH
authors: Mendler
authors: Sebastian
authors: S
authors: Schwind
authors: Heiko
authors: H
authors: Becker
authors: Ann-Kathrin
authors: AK
authors: Eisfeld
authors: Andrew J
authors: AJ
authors: Carroll
authors: Bayard L
authors: BL
authors: Powell
authors: Jonathan E
authors: JE
authors: Kolitz
authors: Ramiro
authors: R
authors: Garzon
authors: Michael A
authors: MA
authors: Caligiuri
authors: Richard M
authors: RM
authors: Stone
authors: Clara D
authors: CD
authors: Bloomfield
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D003582:Cytogenetics / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D012307:Risk Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C524942:MIRN155 microRNA, human; D035683:MicroRNAs
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