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@article{1660276,
author = {Herudková, Zdeňka and Čulen, Martin and Folta, Adam and Ježíšková, Ivana and Cerna, Jana and Loja, Tomáš and Tom, Nikola and Smejkal, Jiri and Semerád, Lukáš and Dvořáková, Dana and Mayer, Jiří and Ráčil, Zdeněk},
article_location = {Hoboken},
article_number = {4},
doi = {http://dx.doi.org/10.1111/bjh.16341},
keywords = {acute myeloid leukaemia; mutations; relapse; patient-derived xenograft; clonality},
language = {eng},
issn = {0007-1048},
journal = {British journal of haematology},
title = {Clonal hierarchy of main molecular lesions in acute myeloid leukaemia},
url = {https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.16341},
volume = {190},
year = {2020}
}
TY - JOUR
ID - 1660276
AU - Herudková, Zdeňka - Čulen, Martin - Folta, Adam - Ježíšková, Ivana - Cerna, Jana - Loja, Tomáš - Tom, Nikola - Smejkal, Jiri - Semerád, Lukáš - Dvořáková, Dana - Mayer, Jiří - Ráčil, Zdeněk
PY - 2020
TI - Clonal hierarchy of main molecular lesions in acute myeloid leukaemia
JF - British journal of haematology
VL - 190
IS - 4
SP - 562-572
EP - 562-572
PB - Wiley-Blackwell
SN - 00071048
KW - acute myeloid leukaemia
KW - mutations
KW - relapse
KW - patient-derived xenograft
KW - clonality
UR - https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.16341
L2 - https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.16341
N2 - 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.
ER -
HERUDKOVÁ, Zdeňka, Martin ČULEN, Adam FOLTA, Ivana JEŽÍŠKOVÁ, Jana CERNA, Tomáš LOJA, Nikola TOM, Jiri SMEJKAL, Lukáš SEMERÁD, Dana DVOŘÁKOVÁ, Jiří MAYER and Zdeněk RÁČIL. Clonal hierarchy of main molecular lesions in acute myeloid leukaemia. \textit{British journal of haematology}. Hoboken: Wiley-Blackwell, vol.~190, No~4, p.~562-572. ISSN~0007-1048. doi:10.1111/bjh.16341. 2020.
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