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Journal of Cancer Research and Clinical Oncology

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02.05.2018 | Original Article – Cancer Research

The influence of mutational status and biological characteristics of acute myeloid leukemia on xenotransplantation outcomes in NOD SCID gamma mice

verfasst von: Martin Culen, Zdenka Kosarova, Ivana Jeziskova, Adam Folta, Jana Chovancova, Tomas Loja, Nikola Tom, Vojtech Bystry, Veronika Janeckova, Dana Dvorakova, Jiri Mayer, Zdenek Racil

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 7/2018

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Titel: The influence of mutational status and biological characteristics of acute myeloid leukemia on xenotransplantation outcomes in NOD SCID gamma mice
verfasst von: Martin Culen
Zdenka Kosarova
Ivana Jeziskova
Adam Folta
Jana Chovancova
Tomas Loja
Nikola Tom
Vojtech Bystry
Veronika Janeckova
Dana Dvorakova
Jiri Mayer
Zdenek Racil
Publikationsdatum: 02.05.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 7/2018
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-018-2652-2

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The influence of mutational status and biological characteristics of acute myeloid leukemia on xenotransplantation outcomes in NOD SCID gamma mice

Abstract

Purpose

Methods

Results

Conclusions

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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