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

Am J Clin Pathol. 2011 Jan;135(1):35-45. doi: 10.1309/AJCPD7NR2RMNQDVF.

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%.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Marrow Cells / chemistry
  • Bone Marrow Cells / pathology
  • DNA Mutational Analysis
  • DNA, Neoplasm / analysis
  • Female
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Nucleophosmin
  • Young Adult

Substances

  • DNA, Neoplasm
  • NPM1 protein, human
  • Nucleophosmin
  • IDH2 protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human