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Página principal > Artículos > Artículos publicados > Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1 |
Fecha: | 2022 |
Resumen: | 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 (FLT3 WT)/low ITD ratio (FLT3 low). Because the comutation of DNMT3A (DNMT3A mut) has been suggested to negatively influence prognosis in AML- NPM1, 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 (FLT3 WT = FLT3 low > 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. |
Ayudas: | Agència de Gestió d'Ajuts Universitaris i de Recerca SLT002/16/0043 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-139 Instituto de Salud Carlos III PI17/01246 Instituto de Salud Carlos III PI20/01621 Instituto de Salud Carlos III CM20/00061 |
Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Publicado en: | Blood advances, Vol. 6 (february 2022) , p. 882-890, ISSN 2473-9537 |
9 p, 1.2 MB |