Identification of a risk dependent microRNA expression signature in myelodysplastic syndromes
| Autor: | Sokol, L, Caceres, G, Volinia, Stefano, Alder, H, Nuovo, Gj, Liu, Cg, Mcgraw, K, Clark, Ja, Sigua, Ca, Chen, Dt, Moscinski, L, Croce, Carlo Maria, List, A. F. |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Aged
80 and over Male Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling MicroRNA Middle Aged Prognosis Article NO Hematopoiesis Gene expression Haematopoiesis International Prognostic Scoring System Myelodysplastic syndromes Leukemia Myeloid Acute MicroRNAs Gene Expression Regulation hemic and lymphatic diseases Myelodysplastic Syndromes Disease Progression Humans Female Epidemiologic Methods Aged Oligonucleotide Array Sequence Analysis |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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