J 2018

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

ČULEN, Martin, Zdeňka KOSAŘOVÁ, Ivana JEŽÍŠKOVÁ, A. FOLTA, Jana CHOVANCOVÁ et. al.

Basic information

Original name

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

Authors

ČULEN, Martin (703 Slovakia, belonging to the institution), Zdeňka KOSAŘOVÁ (203 Czech Republic, belonging to the institution), Ivana JEŽÍŠKOVÁ (203 Czech Republic), A. FOLTA (203 Czech Republic), Jana CHOVANCOVÁ (203 Czech Republic, belonging to the institution), Tomáš LOJA (703 Slovakia, belonging to the institution), Nikola TOM (203 Czech Republic, belonging to the institution), Vojtěch BYSTRÝ (203 Czech Republic, belonging to the institution), V. JANECKOVA (203 Czech Republic), Dana DVOŘÁKOVÁ (203 Czech Republic, belonging to the institution), Jiří MAYER (203 Czech Republic, belonging to the institution) and Zdeněk RÁČIL (203 Czech Republic, guarantor, belonging to the institution)

Edition

Journal of cancer research and clinical oncology, New York, Springer-Verlag, 2018, 0171-5216

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 3.332

RIV identification code

RIV/00216224:14110/18:00103216

Organization unit

Faculty of Medicine

UT WoS

000435380600004

Keywords in English

AML; Engraftment; NOD SCID gamma; Mutations; Sequencing

Tags

International impact, Reviewed
Změněno: 2/5/2019 13:30, Soňa Böhmová

Abstract

V originále

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.

Links

MUNI/A/0968/2017, interní kód MU
Name: Nové přístupy ve výzkumu, diagnostice a terapii hematologických malignit V (Acronym: VýDiTeHeMA V)
Investor: Masaryk University, Category A
NV15-25809A, research and development project
Name: Národní program studia mutací a klonality leukemických buněk u pacientů s akutní myeloidní leukémií