Informace o publikaci

Clonal hierarchy of main molecular lesions in acute myeloid leukaemia

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HERUDKOVÁ Zdeňka ČULEN Martin FOLTA Adam JEŽÍŠKOVÁ Ivana CERNA Jana LOJA Tomáš TOM Nikola SMEJKAL Jiri SEMERÁD Lukáš DVOŘÁKOVÁ Dana MAYER Jiří RÁČIL Zdeněk

Rok publikování 2020
Druh Článek v odborném periodiku
Časopis / Zdroj British journal of haematology
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
www https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.16341
Doi http://dx.doi.org/10.1111/bjh.16341
Klíčová slova acute myeloid leukaemia; mutations; relapse; patient-derived xenograft; clonality
Popis Genetic mutations in acute myeloid leukaemia (AML) are assumed to occur in a sequential order; however, the predominant hierarchical roles of specific mutated genes have not been fully described. In this study, we aimed to determine the clonal involvement of the most frequent AML-associated mutations. Using a targeted sequencing panel for 18 genes, we traced changes and relative clonal contribution of mutations in 52 patients. We analysed 35 pairs of diagnosis and relapse samples, 27 pairs of primary samples and corresponding patient-derived xenografts, and 34 pairs of total leukocytes and corresponding isolated primitive cells or blast populations. In both relapse and xenografts, we observed conservation of main leukaemic clones and variability was limited to subclones with late-acquired mutations. AML evolution thus mainly involved modification of subclones while the clonal background remained unchanged. NPM1 mutations were identified as the most probable leukaemia-transformation lesion, remaining conserved in contrast to high variation of accompanying subclonal FLT3 and NRAS mutations. DNMT3A mutations represented the most stable mutations forming a preleukaemic background in most samples. Mutations in genes IDH1/2, TET2, RUNX1, ASXL1 and U2AF1 were detected both as preleukaemic and as subclonal lesions, suggesting a non-specific order of acquisition.
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