Single-center, observational study of AML/MDS-EB with IDH1/2 mutations: genetic profile, immunophenotypes, mutational kinetics and outcomes.
Hematology
; 28(1): 2180704, 2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-36815747
ABSTRACT
OBJECTIVE:
IDH1/2 mutations, intervening in epigenetic procedures, are frequently encountered in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Knowledge of the genetics, immunophenotypes, and mutational kinetics of IDH1/2-mutated AML can contribute to the understanding of AML clonal architecture and inform therapeutics and monitoring.METHODS:
We retrospectively analyzed 50 IDH1/2-mutated AML/MDS-EB cases of our institution, to identify recurrent co-mutations, immunophenotypes, patterns of co-variance of IDH1/2 allele burdens with those of recurrent co-mutations, frequency of persistent IDH1/2 mutation as clonal hematopoiesis of indeterminate potential (CHIP) in remission and response to hypomethylating agents.RESULTS:
Most frequently co-mutated genes were DNMT3A, SRSF2 and NPM1. Most cases with co-existent IDH1/2 and NPM1 mutations (11/13) showed an 'APL-like' immunophenotype (CD34-HLADR-). Allele burdens of mutated IDH1/2 were identical to mutated SRSF2 allele burdens at diagnosis and remission, but not always to mutated NPM1 allele burden in remission. We show persistence of significant mutIDH1/2 allele burden in approximately one-fourth of patients with deep remissions. IDH1/2 mutations were significantly more frequent among responders to first-line HMA-based regimens than among non-responders, in patients treated for myeloid neoplasms with excess blasts.CONCLUSIONS:
IDH1/2 mutations are most frequently accompanied by DNMT3A, SRSF2 and NPM1 mutations. NPM1-IDH1/2 mutated AML has a mature phenotype possibly amenable to differentiation therapies. IDH1/2 and SRSF2 mutations probably arise at the same developmental stage of the disease, as their allele burdens covariate. IDH1/2 mutation represents CHIP in a substantial proportion of cases and is therefore no reliable residual disease marker. The preferential presence of IDH1/2 mutations among HMA-responders could inform therapeutic decisions if confirmed in larger series.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Síndromes Mielodisplásicas
/
Leucemia Mieloide Aguda
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Hematology
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Suíça