Evaluation of mutations in the isocitrate dehydrogenase genes in therapy-related and secondary acute myeloid leukaemia identifies a patient with clonal evolution to IDH2 R172K homozygosity due to uniparental disomy.

摘要

After their initial identification in high-grade gliomas, acquired heterozygous mutations in the NADPH-dependent isocitrate dehydrogenase (IDH) 1 and 2 genes (IDH1, IDH2) were recently described in patients with de novo acute myeloid leukaemia (AML) (Mardis et al, 2009) and leukaemic transformation of JAK2 mutation positive myeloproliferative neoplasms (Green & Beer, 2010). These mutations lead to the substitution of arginines in the catalytic site of IDH1/2 resulting in neomorphic enzyme activity with accumulation of 2-hydroxyglutarate (Dang et al, 2009; Gross et al, 2010; Ward et al, 2010). To determine the frequency and pathogenetic impact of these mutations in patients with therapy-related AML (t-AML) or secondary AML (sAML) evolved from myelodysplastic syndromes (MDS), we performed a muta-tional analysis of the affected arginine residues in the IDH1 and IDH2 genes in 101 individuals with these disorders. Demographic and clinical characteristics of this cohort are presented in Table SI.