Acute myeloid leukemia with IDH1 or IDH2 mutation: frequency and clinicopathologic features

Abstract

Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are reported in acute myeloid leukemia (AML). We studied the frequency and the clinicopathologic features of IDH1 and IDH2 mutations in AML. Mutations in IDH1 (IDH1(R)¹³²) and IDH2 (IDH2(R)¹⁷²) were assessed by Sanger sequencing in 199 AML cases. Point mutations in IDH1(R)¹³² were detected in 12 (6.0%) of 199 cases and in IDH2(R)¹⁷² in 4 (2.0%) of 196 cases. Of the 16 mutated cases, 15 (94%) were cytogenetically normal, for an overall frequency in this group of 11.8%. IDH1(R)¹³² and IDH2(R)¹⁷² mutations were mutually exclusive. Concurrent mutations in NPM1, FLT3, CEBPA, and NRAS were detected only in AML with the IDH1(R)¹³² mutation. The clinical and laboratory variables of patients with AML with IDH mutations showed no significant differences compared with patients with wild-type IDH. We conclude that IDH1(R)¹³² and IDH2(R)¹⁷² mutations occur most often in cytogenetically normal AML cases with an overall frequency of approximately 11.8%.

Figure 1. Detection of IDH1 ^R132 mutation by Sanger sequencing

Sanger-sequencing showing (A) wild-type IDH1 codon 132: CGT, R132; (B) wild-type IDH2 codon 172: AGG, R172; (C) mutant IDH1 codon 132: TGT, R132C and (D) mutant IDH2 codon 172: AAG, R172K. Note that both IDH1^R132 and IDH2^R172 mutations are heterozygous missense point mutations.