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Identification of a risk dependent microRNA expression signature in myelodysplastic syndromes
Author(s) -
Sokol Lubomir,
Caceres Gisela,
Volinia Stefano,
Alder Hans,
Nuovo Gerard J.,
Liu ChangGong,
McGraw Kathy,
Clark Justine A.,
Sigua Celia A.,
Chen DungTsa,
Moscinski Lynn,
Croce Carlo M.,
List Alan F.
Publication year - 2011
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2011.08581.x
Subject(s) - myelodysplastic syndromes , microrna , oncology , medicine , international prognostic scoring system , myeloid , hematology , haematopoiesis , progenitor cell , survival analysis , biology , stem cell , bone marrow , gene , genetics
Summary 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.