An advanced preclinical mouse model for acute myeloid leukemia using patients' cells of various genetic subgroups and in vivo bioluminescence imaging

PloS One
Binje VickIrmela Jeremias

Abstract

Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous disease with poor outcome. Adequate model systems are required for preclinical studies to improve understanding of AML biology and to develop novel, rational treatment approaches. Xenografts in immunodeficient mice allow performing functional studies on patient-derived AML cells. We have established an improved model system that integrates serial retransplantation of patient-derived xenograft (PDX) cells in mice, genetic manipulation by lentiviral transduction, and essential quality controls by immunophenotyping and targeted resequencing of driver genes. 17/29 samples showed primary engraftment, 10/17 samples could be retransplanted and some of them allowed virtually indefinite serial transplantation. 5/6 samples were successfully transduced using lentiviruses. Neither serial transplantation nor genetic engineering markedly altered sample characteristics analyzed. Transgene expression was stable in PDX AML cells. Example given, recombinant luciferase enabled bioluminescence in vivo imaging and highly sensitive and reliable disease monitoring; imaging visualized minimal disease at 1 PDX cell in 10000 mouse bone marrow cells and facilitated quantifying leu...Continue Reading

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Citations

Dec 20, 2016·Nature Medicine·Constanze SchneiderJindrich Cinatl
Feb 15, 2016·Clinical Pharmacology and Therapeutics·E IzumchenkoD Sidransky
May 23, 2018·International Journal of Cancer. Journal International Du Cancer·Bettina von NeubeckReinhard Zeidler
Sep 21, 2018·Leukemia & Lymphoma·Birgitta Christine HecklIrmela Jeremias
Mar 1, 2018·Oncogene·Amina M Abdul-AzizStuart A Rushworth
Sep 1, 2019·Genes, Chromosomes & Cancer·Martin Chopra, Stefan K Bohlander
Oct 27, 2015·Oncotarget·Siwei ZhangJohanna Liebl
Jun 16, 2019·Leukemia·Sophie M StiefKarsten Spiekermann
Jun 28, 2020·Leukemia·Patrizia JensenStefan Fröhling
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Jan 10, 2019·Cancer Research·Christopher R MarleinStuart A Rushworth
Jan 26, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Luke JonesRichard B Lock

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Methods Mentioned

BETA
xenograft
flow cytometry
xenografts
transgenic
FACS
bioluminescence imaging

Software Mentioned

BWA
ELDA
VarScan
Excel

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