Nucleophosmin1 and isocitrate dehydrogenase 1 and 2 as measurable residual disease markers in acute myeloid leukemia
| Autor: | Gabor Mikala, András Kozma, Ágnes Király, Péter Reményi, Hajnalka Andrikovics, András Bors, István Vályi-Nagy, Petra Kövy, János Dolgos, Viktor Lakatos, László Gopcsa, Zoltán Őrfi, Nóra Lovas, József Harasztdombi |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Oncology Cell Transplantation Epidemiology medicine.medical_treatment Gene Identification and Analysis Artificial Gene Amplification and Extension Hematopoietic stem cell transplantation Gene mutation Polymerase Chain Reaction Hematologic Cancers and Related Disorders hemic and lymphatic diseases Medicine and Health Sciences Blood and Lymphatic System Procedures Frameshift Mutation Aged 80 and over Leukemia Multidisciplinary Hematopoietic Stem Cell Transplantation Nuclear Proteins Myeloid leukemia Hematology Middle Aged Myeloid Leukemia Isocitrate Dehydrogenase Leukemia Myeloid Acute Treatment Outcome Isocitrate dehydrogenase Medicine Female Nucleophosmin Research Article Acute Myeloid Leukemia Adult Genetic Markers medicine.medical_specialty NPM1 IDH1 Adolescent Science Surgical and Invasive Medical Procedures Research and Analysis Methods IDH2 Young Adult Internal medicine Genetics medicine Humans Molecular Biology Techniques Mutation Detection Molecular Biology Aged Transplantation business.industry Cancers and Neoplasms Biology and Life Sciences medicine.disease Survival Analysis Medical Risk Factors Mutation business Stem Cell Transplantation |
| Zdroj: | PLoS ONE, Vol 16, Iss 6, p e0253386 (2021) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Monitoring measurable residual disease (MRD) in acute myeloid leukemia (AML) plays an important role in predicting relapse and outcome. The applicability of the leukemia-initiating nucleophosmin1 (NPM1) gene mutations in MRD detection is well-established, while that of isocitrate dehydrogenase1/2 (IDH1/2) mutations are matter of debate. The aim of this study was to investigate the stability of NPM1 and IDH1/2 mutations at diagnosis and relapse retrospectively in 916 adult AML patients. The prognostic value of MRD was evaluated by droplet digital PCR on the DNA level in a selected subgroup of patients in remission. NPM1 re-emerged at relapse in 91% (72/79), while IDH1/2 in 87% (20/23) of mutation-positive cases at diagnosis. NPM1 mutation did not develop at relapse, on the contrary novel IDH1/2 mutations occurred in 3% (3/93) of previously mutation-negative cases. NPM1 MRD-positivity after induction (n = 116) proved to be an independent, adverse risk factor (MRDpos 24-month OS: 39.3±6.2% versus MRDneg: 58.5±7.5%, p = 0.029; HR: 2.16; 95%CI: 1.25–3.74, p = 0.006). In the favorable subgroup of mutated NPM1 without fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) or with low allelic ratio, NPM1 MRD provides a valuable prognostic biomarker (NPM1 MRDpos versus MRDneg 24-month OS: 42.9±6.7% versus 66.7±8.6%; p = 0.01). IDH1/2 MRD-positivity after induction (n = 62) was also associated with poor survival (MRDpos 24-month OS: 41.3±9.2% versus MRDneg: 62.5±9.0%, p = 0.003; HR 2.81 95%CI 1.09–7.23, p = 0.032). While NPM1 variant allele frequency decreased below 2.5% in remission in all patients, IDH1/2 mutations (typically IDH2 R140Q) persisted in 24% of cases. Our results support that NPM1 MRD even at DNA level is a reliable prognostic factor, while IDH1/2 mutations may represent pre-leukemic, founder or subclonal drivers. |
| Databáze: | OpenAIRE |
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