Prognostic significance of mutation profile at diagnosis and mutation persistence during disease remission in adult acute myeloid leukaemia patients

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Publikace nespadá pod Ekonomicko-správní fakultu, ale pod Lékařskou fakultu. Oficiální stránka publikace je na webu muni.cz.
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FOLTA Adam ČULEN Martin JEŽÍŠKOVÁ Ivana HERUDKOVÁ Zdeňka TOM Nikola HLUBINKOVÁ Tereza JANEČKOVÁ Veronika ĎURINÍKOVÁ Anna VYDRA Jan SEMERÁD Lukáš DVOŘÁKOVÁ Dana REMEŠOVÁ Hana CEROVSKÁ Ela CETKOVSKÝ Petr JINDRA Pavel SZOTKOWSKI Tomáš ŽÁK Pavel MAYER Jiří RÁČIL Zdeněk

Rok publikování 2019
Druh Článek v odborném periodiku
Časopis / Zdroj British journal of haematology
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
www http://dx.doi.org/10.1111/bjh.15916
Doi http://dx.doi.org/10.1111/bjh.15916
Klíčová slova acute myeloid leukaemia; next generation sequencing; persistent mutations; prognostic markers; survival
Popis In this multi-centre study, we analysed the prognostic impact of mutations in 19 genes associated with myeloid malignancies in 258 newly diagnosed acute myeloid leukaemia patients (aged 19-70 years) undergoing intensive therapy. We identified five patient groups with different prognostic risks and different benefits from allogeneic hematopoietic stem cell transplantation (alloHSCT) within the intermediate cytogenetic risk group patients (n = 184). The most adverse prognosis was observed in patients with DNMT3A and FLT3-ITD co-mutation, whose survival could be significantly improved with alloHSCT. In contrast, the most favourable prognosis without any further benefit from alloHSCT was identified in patients with mutations in NPM1 or CEBPA, after exclusion of the unfavourable prognostic groups defined by mutations in DNMT3A, RUNX1 or genes from chromatin/spliceosome group. An additional analysis of 113 diagnosis-remission paired samples revealed that persistence of non-DNMT3A mutations (above 2% VAF) represented a further negative prognostic factor. The proposed model offers a possible molecular stratification and treatment guidance for intermediate cytogenetic risk group patients.
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