科研之友
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摘要
The prognostic value of IDH1 mutations has been systematically evaluated in acute myeloid leukemia (AML) patients recently. However, the role of IDH1 expression in AML is still under exploration. To investigate the clinical significance, we analyzed the IDH1/2 expression in 320 patients with cytogenetically normal AML (CN-AML) by quantitative real-time reverse-transcription polymerase chain reaction. High expression of IDH1 was predominant in patients with FLT3-ITD and DNMT3A mutations and less prevalent in cases with CEBPA double allele mutations. Strong association was observed between high IDH1 expression and low expression of microRNA 181 family. Prognosis was adversely affected by high IDH1 expression, with shorter overall survival and event-free survival in the context of clinical characteristics, including age, WBC count, and gene mutations of NPM1, FLT3-ITD, CEBPA, IDH1, IDH2 and DNMT3A in CN-AML. Moreover, the clinical outcome of IDH1 expression in terms of overall survival, event-free survival and complete remission rate still remained in multivariate models in CN-AML. Importantly, the prognostic value was validated using the published microarray data from 79 adult patients treated according to the German AMLCG-1999 protocol. Our results demonstrated that high IDH1 expression is associated with a poor prognosis of CN-AML. @@@ What's new? Isocitrate dehydrogenase 1 (IDH1) is one of two enzymes that convert isocitrate to alpha-ketoglutarate and play an important role in metabolic reprogramming of tumor cells. Here the authors demonstrate that high IDH1 expression is associated with a poor prognosis for acute myeloid leukemia with normal cytogenetic status (CN-AML). In addition, they evaluated microRNAs known to regulate IDH1 status in bone marrow blasts and found an association between high IDH1 and low microRNA181 expression. These studies link tumor metabolism to the clinical prognosis in patients with CN-AML.
