Recently, recurrent somatic missense mutations in NADP+-dependent isocitrate dehydrogenase gene (IDH1) at codon R132, as well as IDH2 at codon R172, have been identified in low-grade gliomas/secondary glioblastoma by high-throughput sequencing. 1 Subsequent studies also revealed that acquired somatic mutations in IDH1 frequently occurred in adult hematological malignancies, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). 2, 3 More recently, Paschka et al. 4reported that not only IDH1 but also IDH2 mutations occurred relatively frequently in adult AML, and that these mutations were associated with older age, poor prognosis, cytogenetically normal AML (CN-AML) and the genotype of mutated NPM1 without FLT3-internal tandem duplication (ITD). Exon 4 of both IDH1 and IDH2, which was previously identified as a hot spot for mutations in these genes, encodes three arginine residues (R100, R109 and R132 in IDH1 and R140, R149, and R172 in IDH2) that are important for protein activities. 5 Tumor-derived IDH1 and IDH2 mutations impair the affinity of enzymes for substrates, and dominantly inhibit wild-type IDH1 and IDH2 activities through the formation of catalytically inactive heterodimers. 5 Ho et al. 6 previously reported that IDH1 mutations are not detected in pediatric AML; however, little is known about the incidence and prognostic values of IDH1 and IDH2 mutations in pediatric myeloid malignancies. Here, we analyzed mutations that involve the activation sites of IDH1 and IDH2 (exon 4 and exon 7 in both IDH1 and IDH2) using genomic DNA-polymerase chain reaction amplification/sequencing in a total of 199 samples of pediatric myeloid malignancies, including 17 AML-derived cell lines, 115 primary cases of AML, 28 primary cases of MDS, 15 primary cases of juvenile myelomonocytic leukemia (JMML), 6 chronic myeloid leukemia (CML)-derived cell lines and 18 primary cases of CML. Moreover, to assess whether IDH1 and IDH2 mutations overlap with known gene abnormalities, such as FLT3, c-KIT and NPM1 mutations, mutational analyses of FLT3, c-KIT and NPM1 were also performed in AML samples. This study was approved by the ethics committee of the University of Tokyo (Approval Number 3043).

The common IDH2 R140Q mutation was detected in a single AML case, whereas no IDH1 mutation including G123E, as well as no other IDH2 mutations, such as R172K, were detected in our study (Figure 1). The IDH2 R140Q mutation detected in the AML case was a heterozygous substitution. No IDH1 and IDH2 mutations were detected in the JMML, MDS or CML samples examined. As the additional activation sites of both IDH1 and