In:
Journal of Hematology & Oncology, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2021-12)
Abstract:
IDH1 and IDH2 mutations (IDH1/2 Mut ) 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 Mut 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 Mut . Mutational patterns of IDH1/2 Mut in T-ALL present some specific features compared to AML. Whereas IDH2 R140Q mutation was frequent in T-ALL (25 of 51 mutations), the IDH2 R172 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 Mut 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.
Type of Medium:
Online Resource
ISSN:
1756-8722
DOI:
10.1186/s13045-021-01068-4
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
2429631-4