Single-center, observational study of AML/MDS-EB with IDH1/2 mutations: genetic profile, immunophenotypes, mutational kinetics and outcomes
ABSTRACTObjective 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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Hematology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/16078454.2023.2180704 |
| _version_ | 1797895850500816896 |
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| author | Vasiliki Papadopoulou Jacqueline Schoumans Valentin Basset Françoise Solly Jérôme Pasquier Sabine Blum Olivier Spertini |
| author_facet | Vasiliki Papadopoulou Jacqueline Schoumans Valentin Basset Françoise Solly Jérôme Pasquier Sabine Blum Olivier Spertini |
| author_sort | Vasiliki Papadopoulou |
| collection | DOAJ |
| description | ABSTRACTObjective 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. |
| first_indexed | 2024-04-10T07:32:18Z |
| format | Article |
| id | doaj.art-99facb9da5df438db2322ef2e2c1fba5 |
| institution | Directory Open Access Journal |
| issn | 1607-8454 |
| language | English |
| last_indexed | 2024-04-10T07:32:18Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Hematology |
| spelling | doaj.art-99facb9da5df438db2322ef2e2c1fba52023-02-23T13:32:09ZengTaylor & Francis GroupHematology1607-84542023-12-0128110.1080/16078454.2023.2180704Single-center, observational study of AML/MDS-EB with IDH1/2 mutations: genetic profile, immunophenotypes, mutational kinetics and outcomesVasiliki Papadopoulou0Jacqueline Schoumans1Valentin Basset2Françoise Solly3Jérôme Pasquier4Sabine Blum5Olivier Spertini6Service and Laboratory of Hematology, Department of Oncology, Lausanne University Hospital, Lausanne, SwitzerlandService and Laboratory of Hematology, Department of Oncology, Lausanne University Hospital, Lausanne, SwitzerlandService and Laboratory of Hematology, Department of Oncology, Lausanne University Hospital, Lausanne, SwitzerlandService and Laboratory of Hematology, Department of Oncology, Lausanne University Hospital, Lausanne, SwitzerlandCenter for Primary Care and Public Health, University of Lausanne, Lausanne, SwitzerlandService and Laboratory of Hematology, Department of Oncology, Lausanne University Hospital, Lausanne, SwitzerlandService and Laboratory of Hematology, Department of Oncology, Lausanne University Hospital, Lausanne, SwitzerlandABSTRACTObjective 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.https://www.tandfonline.com/doi/10.1080/16078454.2023.2180704Acute myeloid leukemiaIDH1/2Double-negative phenotypeCHIP |
| spellingShingle | Vasiliki Papadopoulou Jacqueline Schoumans Valentin Basset Françoise Solly Jérôme Pasquier Sabine Blum Olivier Spertini Single-center, observational study of AML/MDS-EB with IDH1/2 mutations: genetic profile, immunophenotypes, mutational kinetics and outcomes Hematology Acute myeloid leukemia IDH1/2 Double-negative phenotype CHIP |
| title | Single-center, observational study of AML/MDS-EB with IDH1/2 mutations: genetic profile, immunophenotypes, mutational kinetics and outcomes |
| title_full | Single-center, observational study of AML/MDS-EB with IDH1/2 mutations: genetic profile, immunophenotypes, mutational kinetics and outcomes |
| title_fullStr | Single-center, observational study of AML/MDS-EB with IDH1/2 mutations: genetic profile, immunophenotypes, mutational kinetics and outcomes |
| title_full_unstemmed | Single-center, observational study of AML/MDS-EB with IDH1/2 mutations: genetic profile, immunophenotypes, mutational kinetics and outcomes |
| title_short | Single-center, observational study of AML/MDS-EB with IDH1/2 mutations: genetic profile, immunophenotypes, mutational kinetics and outcomes |
| title_sort | single center observational study of aml mds eb with idh1 2 mutations genetic profile immunophenotypes mutational kinetics and outcomes |
| topic | Acute myeloid leukemia IDH1/2 Double-negative phenotype CHIP |
| url | https://www.tandfonline.com/doi/10.1080/16078454.2023.2180704 |
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