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@article{1423213,
author = {Čulen, Martin and Kosařová, Zdeňka and Ježíšková, Ivana and Folta, A. and Chovancová, Jana and Loja, Tomáš and Tom, Nikola and Bystrý, Vojtěch and Janeckova, V. and Dvořáková, Dana and Mayer, Jiří and Ráčil, Zdeněk},
article_location = {New York},
article_number = {7},
doi = {http://dx.doi.org/10.1007/s00432-018-2652-2},
keywords = {AML; Engraftment; NOD SCID gamma; Mutations; Sequencing},
language = {eng},
issn = {0171-5216},
journal = {Journal of cancer research and clinical oncology},
title = {The influence of mutational status and biological characteristics of acute myeloid leukemia on xenotransplantation outcomes in NOD SCID gamma mice},
volume = {144},
year = {2018}
}
TY - JOUR
ID - 1423213
AU - Čulen, Martin - Kosařová, Zdeňka - Ježíšková, Ivana - Folta, A. - Chovancová, Jana - Loja, Tomáš - Tom, Nikola - Bystrý, Vojtěch - Janeckova, V. - Dvořáková, Dana - Mayer, Jiří - Ráčil, Zdeněk
PY - 2018
TI - The influence of mutational status and biological characteristics of acute myeloid leukemia on xenotransplantation outcomes in NOD SCID gamma mice
JF - Journal of cancer research and clinical oncology
VL - 144
IS - 7
SP - 1239-1251
EP - 1239-1251
PB - Springer-Verlag
SN - 01715216
KW - AML
KW - Engraftment
KW - NOD SCID gamma
KW - Mutations
KW - Sequencing
N2 - This study aimed at analyzing the association of gene mutations and other acute myeloid leukemia (AML) characteristics with engraftment outcomes in immunodeficient mice and to select the engraftment outcomes that best reflect patient survival. Mutations in 19 genes as well as leukemia- and patient-related characteristics were analyzed for a group of 47 de novo AML samples with respect to three engraftment outcomes: engraftment ability, engraftment intensity (percentage of hCD45(+) cells) and engraftment latency. Leukemia-related characteristics were additionally analyzed in an extended group of 68 samples that included the 47 de novo samples, and additional 21 samples from refractory and relapsed cases. Engraftment outcomes were compared with overall and event-free survival of the patients. For the 47 de novo samples, no single mutation influenced engraftment, whereas the NPM1 (mut) /DNMT3A (mut) co-mutation was associated with higher engraftment ability. NPM1 (mut) /FLT3-ITD (neg) had lower engraftment intensity. Among leukemia-related characteristics, a complex karyotype was associated with higher engraftment intensity. Among patient-related characteristics, higher cytogenetic risk was associated with higher engraftment intensity, and failure to achieve clinical remission was associated with shorter engraftment latency. In the extended group of 68 samples, white blood count was associated with higher engraftment ability, and the presence of a complex karyotype was associated with higher engraftment intensity. Association with patient overall survival was seen only for engraftment intensity. The engraftment of AML was influenced by mutation-interactions and other AML characteristics, rather than by single mutated genes, and engraftment intensity best reflected clinical penetrance of AML.
ER -
ČULEN, Martin, Zdeňka KOSAŘOVÁ, Ivana JEŽÍŠKOVÁ, A. FOLTA, Jana CHOVANCOVÁ, Tomáš LOJA, Nikola TOM, Vojtěch BYSTRÝ, V. JANECKOVA, Dana DVOŘÁKOVÁ, Jiří MAYER and Zdeněk RÁČIL. The influence of mutational status and biological characteristics of acute myeloid leukemia on xenotransplantation outcomes in NOD SCID gamma mice. \textit{Journal of cancer research and clinical oncology}. New York: Springer-Verlag, 2018, vol.~144, No~7, p.~1239-1251. ISSN~0171-5216. Available from: https://dx.doi.org/10.1007/s00432-018-2652-2.
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