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Title: | Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1 |
Author: | Oñate, Guadalupe Bataller, Alex Garrido, Ana Hoyos Colell, Montserrat Arnan, Montserrat Vives, Susana Coll, Rosa Tormo, Mar Sampol, Antonia Escoda, Lourdes Salamero, Olga Garcia, Antoni Bargay, Joan Aljarilla, Alba Nomdedeu, Josep F. Esteve, Jordi Sierra, Jorge Pratcorona, Marta |
Keywords: | Leucèmia mieloide Enzims Myeloid leukemia Enzymes |
Issue Date: | 13-Sep-2021 |
Publisher: | American Society of Hematology |
Abstract: | The negative prognostic impact of internal tandem duplication of FLT3 (FLT3-ITD) in patients with acute myeloid leukemia with mutated NPM1 (AML-NPM1) is restricted to those with a higher FLT3-ITD allelic ratio (FLT3(high); >= 0.5) and considered negligible in those with a wild-type (FLT3WT)/low ITD ratio (FLT3low). Because the comutation of DNMT3A (DNMT3A(mut)) has been suggested to negatively influence prognosis in AMLNPM1, we analyzed the impact of DNMT3A(mut) in FLT3-ITD subsets (absent, low, and high ratios). A total of 164 patients diagnosed with AML-NPM1 included in 2 consecutive CETLAM protocols and with DNMT3A and FLT3 status available were studied. Overall, DNMT3A(mut) status did not have a prognostic impact, with comparable overall survival (P = .2). Prognostic stratification established by FLT3-ITD (FLT3WT = FLT3low > FLT3(high)) was independent of DNMT3A(mut) status. Measurable residual disease (MRD) based on NPM1 quantitative polymerase chain reaction was available for 94 patients. DNMT3A(mut) was associated with a higher number of mutated NPM1 transcripts after induction (P = .012) and first consolidation (C1; P < .001). All DNMT3A(mut) patients were MRD+ after C1 (P < .001) and exhibited significant MRD persistence after C2 and C3 (MRD+ vs MRD-; P = .027 and P = .001, respectively). Finally, DNMT3A(mut) patients exhibited a trend toward greater risk of molecular relapse (P = .054). In conclusion, DNMT3A(mut) did not modify the overall prognosis exerted by FLT3-ITD in AML-NPM1 despite delayed MRD clearance, possibly because of MRD-driven preemptive intervention. |
Note: | Reproducció del document publicat a: https://doi.org/10.1182/bloodadvances.2020004136 |
It is part of: | Blood Advances, 2021, vol 6, num 3, p. 882-890 |
URI: | http://hdl.handle.net/2445/183760 |
Related resource: | https://doi.org/10.1182/bloodadvances.2020004136 |
ISSN: | 2473-9537 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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