High IDH1 expression is associated with a poor prognosis in cytogenetically normal acute myeloid leukemia

Abstract

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.

Characterization of TET and IDH gene expression in chronic lymphocytic leukemia: comparison with normal B cells and prognostic significance

“…TET2 was decreased in cervical squamous cell carcinoma along with %5-hmC, and low levels in patients were shown to be associated with a poor prognosis [52]. In contrast to our results, another team observed that high expression of IDH1 is associated with shorter overall survival in cytogenetically normal acute myeloid leukemia [53]. In epithelial ovarian cancer, TET2 and %5-hmC decreased compared with normal controls, and this low expression was associated with poor overall survival of the patients [54].…”

Prognostic impact of MYH9 expression on patients with acute myeloid leukemia

“…Favorable subgroups included t(8;21)/ AML1-ETO and inv16/ CBFβ-MYH11 ; adverse consisted of t(9;22), inv(3)/t(3;3), -5, -7, del(5q), del(7p), 11q23 and complex translocations; intermediate subtype contained cytogenetically normal and AML with other cytogenetic abnormalities. Patients received HAA (homoharringtonin 2 mg/m 2 /day for 7 days, cytarabine 100 mg/m 2 /day for7 days and aclarubicin 20 mg/m 2 /day for 5 days), DA (daunorubicin 45 mg/m 2 /day for 3 days and cytarabine 100 mg/m 2 /day for 7 days) and IA regimen (idarubicin 8–10 mg/m 2 /day for 3 days and cytarabine 150 mg/m 2 /day for 7 days) [2, 19]. In the consolidation therapy, younger patients were treated with a high-dose cytarabine-based chemotherapy [19].…”

“…Patients received HAA (homoharringtonin 2 mg/m 2 /day for 7 days, cytarabine 100 mg/m 2 /day for7 days and aclarubicin 20 mg/m 2 /day for 5 days), DA (daunorubicin 45 mg/m 2 /day for 3 days and cytarabine 100 mg/m 2 /day for 7 days) and IA regimen (idarubicin 8–10 mg/m 2 /day for 3 days and cytarabine 150 mg/m 2 /day for 7 days) [2, 19]. In the consolidation therapy, younger patients were treated with a high-dose cytarabine-based chemotherapy [19]. The chemotherapy consolidation for elderly patients was decided by the physicians in an individualized manner, as described previously [19].…”

“…In the consolidation therapy, younger patients were treated with a high-dose cytarabine-based chemotherapy [19]. The chemotherapy consolidation for elderly patients was decided by the physicians in an individualized manner, as described previously [19]. No patient in our study received allogeneic transplantation.…”

Prognostic significance of huntingtin interacting protein 1 expression on patients with acute myeloid leukemia

“…CN -AML was defined as AML with the karyotype 46, XY [20] or 46 XX [20] in all 20 metaphase cells analyzed. Patients were treated with intensive induction chemotherapy as previous reported2324. In the consolidation therapy, younger patients were treated with a high-dose cytarabine-based chemotherapy23.…”