title: Identification of a risk dependent microRNA expression signature in myelodysplastic syndromes.
abstract: The myelodysplastic syndromes (MDS) display both haematological and biological heterogeneity with variable leukaemia potential. MicroRNAs play an important role in tumour suppression and the regulation of self-renewal and differentiation of haematopoietic progenitors. Using a microarray platform, we evaluated microRNA expression from 44 patients with MDS and 17 normal controls. We identified a thirteen microRNA signature with statistically significant differential expression between normal and MDS specimens (P < 0·01), including down-regulation of members of the leukaemia-associated MIRLET7 family. A unique signature consisting of 10 microRNAs was closely associated with International Prognostic Scoring System (IPSS) risk category permitting discrimination between lower (Low/Intermediate-1) and higher risk (Intermediate-2/High) disease (P < 0·01). Selective overexpression of MIR181 family members was detected in higher risk MDS, indicating pathogenetic overlap with acute myeloid leukaemia. Survival analysis of an independent cohort of 22 IPSS lower risk MDS patients revealed a median survival of 3·5 years in patients with high expression of MIR181 family compared to 9·3 years in patients with low MIR181 expression (P = 0·002). Our pilot study suggested that analysis of microRNA expression profile offers diagnostic utility, and provide pathogenetic and prognostic discrimination in MDS.
authors.affiliation: Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL, USA. lubomir. sokol@moffitt. org
authors.forename: Lubomir
authors.initials: L
authors.lastname: Sokol
authors.forename: Gisela
authors.initials: G
authors.lastname: Caceres
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.forename: Hans
authors.initials: H
authors.lastname: Alder
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Nuovo
authors.forename: Chang-Gong
authors.initials: CG
authors.lastname: Liu
authors.forename: Kathy
authors.initials: K
authors.lastname: McGraw
authors.forename: Justine A
authors.initials: JA
authors.lastname: Clark
authors.forename: Celia A
authors.initials: CA
authors.lastname: Sigua
authors.forename: Dung-Tsa
authors.initials: DT
authors.lastname: Chen
authors.forename: Lynn
authors.initials: L
authors.lastname: Moscinski
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
authors.forename: Alan F
authors.initials: AF
authors.lastname: List
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D004812:Epidemiologic Methods; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs