In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 6 ( 2021-6-21), p. e0253386-
Kurzfassung:
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 (MRD pos 24-month OS: 39.3±6.2% versus MRD neg : 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 MRD pos versus MRD neg 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 (MRD pos 24-month OS: 41.3±9.2% versus MRD neg : 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.
Materialart:
Online-Ressource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0253386
DOI:
10.1371/journal.pone.0253386.g001
DOI:
10.1371/journal.pone.0253386.g002
DOI:
10.1371/journal.pone.0253386.g003
DOI:
10.1371/journal.pone.0253386.g004
DOI:
10.1371/journal.pone.0253386.g005
DOI:
10.1371/journal.pone.0253386.g006
DOI:
10.1371/journal.pone.0253386.g007
DOI:
10.1371/journal.pone.0253386.t001
DOI:
10.1371/journal.pone.0253386.t002
DOI:
10.1371/journal.pone.0253386.s001
DOI:
10.1371/journal.pone.0253386.s002
DOI:
10.1371/journal.pone.0253386.s003
DOI:
10.1371/journal.pone.0253386.s004
DOI:
10.1371/journal.pone.0253386.s005
DOI:
10.1371/journal.pone.0253386.s006
DOI:
10.1371/journal.pone.0253386.s007
DOI:
10.1371/journal.pone.0253386.s008
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2021
ZDB Id:
2267670-3
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