IDH1/2 mutations in acute myeloid leukemia

Abstract

The mutational and epigenetic landscape of acute myeloid leukemia (AML) has become increasingly well understood in recent years, informing on biological targets for precision medicine. Among the most notable findings was the recognition of mutational hot-spots in the isocitrate dehydrogenase (IDH) genes. In this review, we provide an overview on the IDH1/2 mutation landscape in Korean AML patients, and compare it with available public data. We also discuss the role of IDH1/2 mutations as biomarkers and drug targets. Taken together, occurrence of IDH1/2 mutations is becoming increasingly important in AML treatment, thus requiring thorough examination and follow-up throughout the clinical course of the disease.

Keywords: Acute myeloid leukemia; Biomarker; Drug target; IDH; Korean.

Fig. 1

(A) Oncoprint with mutation-profiled Korean acute myeloid leukemia samples. Blue: missense mutation, pink: frameshift insertion, sky blue: frameshift deletion, and green: multi-hit. Mutations listed in the COSMIC database are marked with grey dots. (B) Oncoprint obtained from cBioPortal. Clinical and genomic data (622 from OHSU and 200 from TCGA) were merged.

Fig. 2

(A) Co-occurrence plot displaying interactions between genes in Korean patients. Red indicates higher degree of co-occurrence between two genes, while blue indicates higher degree of mutual exclusiveness. P-values from each Fisher’s exact test are grouped into five groups, and the groups with P>0.05 are not displayed. The remaining four groups with P<0.05 are displayed on a scale for each section. In the case that the absolute value of log₂ odds ratio was at least 1 and the P-value is marked, the box’s margin is marked black. When mutations of two genes did not occur in one sample, the odds ratio could not be calculated, therefore, many mutual exclusive interactions identified in Fig. 1A are not shown in this plot. (B) Co-occurrence plot using publicly available data matching with Fig. 1B. The number of patients is larger than the Korean cohort. Accordingly, a higher number of mutually exclusive signals were detected in the public database than in the Korean cohort.

Fig. 3

(A) Oncoplot showing Korean patients with FLT3, NPM1, DNMT3A, IDH1 and IDH2 mutations. Hotspots are shown for IDH1 and IDH2. (B) Interactions between five genes from Korean AML patients shown in the same way as previously displayed. (C) Oncoplots using public data from cBioPortal regarding five genes. (D) Interactions between five genes from samples from cBioPortal shown in the same way as previously displayed. In cases of white color boxes and P-value marking, odds ratio is zero because there are no events of mutations in both genes.