Oncogenetic landscape and clinical impact of IDH1 and IDH2 mutations in T-ALL.
(2021) Journal of Hematology & Oncology — Vol. 14, n° 1, p. 74 [1-7] (2021)
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- IDH1 and IDH2 mutations (IDH1/2) are recognized as recurrent genetic alterations in acute myeloid leukemia (AML) and associated with both clinical impact and therapeutic opportunity due to the recent development of specific IDH1/2 inhibitors. In T-cell acute lymphoblastic leukemia (T-ALL), their incidence and prognostic implications remain poorly reported. Our targeted next-generation sequencing approach allowed comprehensive assessment of genotype across the entire IDH1 and IDH2 locus in 1085 consecutive unselected and newly diagnosed patients with T-ALL and identified 4% of, virtually exclusive (47 of 49 patients), IDH1/2. Mutational patterns of IDH1/2 in T-ALL present some specific features compared to AML. Whereas IDH2 mutation was frequent in T-ALL (25 of 51 mutations), the IDH2 AML hotspot was absent. IDH2 mutations were associated with older age, an immature phenotype, more frequent RAS gain-of-function mutations and epigenetic regulator loss-of-function alterations (DNMT3A and TET2). IDH2 mutations, contrary to IDH1 mutations, appeared to be an independent prognostic factor in multivariate analysis with the NOTCH1/FBXW7/RAS/PTEN classifier. IDH2 were significantly associated with a high cumulative incidence of relapse and very dismal outcome, suggesting that IDH2-mutated T-ALL cases should be identified at diagnosis in order to benefit from therapeutic intensification and/or specific IDH2 inhibitors.
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Simonin, M., Schmidt, A., Bontoux, C., Dourthe, M.-É., Lengliné, E., Andrieu, G. P., Lhermitte, L., Graux, C., Grardel, N., Cayuela, J.-M., Huguet, F., Arnoux, I., Ducassou, S., Macintyre, E., Gandemer, V., Dombret, H., Petit, A., Ifrah, N., Baruchel, A., et al. (2021). Oncogenetic landscape and clinical impact of IDH1 and IDH2 mutations in T-ALL. Journal of Hematology & Oncology, 14(1), 74 [1-7]. https://doi.org/10.1186/s13045-021-01068-4 (Original work published 2021)