GEMMs addressing Pax5 loss-of-function in childhood pB-ALL

被引:4
|
作者
Auer, Franziska [1 ]
Ingenhag, Deborah [1 ]
Bhatia, Sanil [1 ]
Enczmann, Juergen [2 ]
Cobaleda, Cesar [3 ]
Sanchez-Garcia, Isidro [4 ,5 ]
Borkhardt, Arndt [1 ]
Hauer, Julia [1 ]
机构
[1] Univ Dusseldorf, Fac Med, Dept Pediat Oncol Hematol & Clin Immunol, Moorenstr 5, D-40225 Dusseldorf, Germany
[2] Univ Dusseldorf, Fac Med, Inst Transplantat Diagnost & Cell Therapeut ITZ, D-40225 Dusseldorf, Germany
[3] Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, Campus Cantoblanco, Madrid, Spain
[4] Univ Salamanca, CSIC, Inst Biol Mol & Celular Canc, Expt Therapeut & Translat Oncol Program, Campus M de Unamuno S-N, E-37008 Salamanca, Spain
[5] Inst Biomed Res Salamanca IBSAL, Salamanca, Spain
基金
美国国家卫生研究院;
关键词
Leukemia; Next generation sequencing; Murine models; Genetic susceptibility; Pax5; ACUTE LYMPHOBLASTIC-LEUKEMIA; B-CELL; LYMPHOID LINEAGE; FUSION PROTEIN; MOUSE MODELS; WILD-TYPE; IN-VITRO; CANCER; MUTATIONS; TEL-AML1;
D O I
10.1016/j.ejmg.2015.11.009
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Germline mutations in transcription factors, which are implicated in hematopoiesis in general or specifically in B-cell differentiation have recently been described to confer an inherited risk to pB-ALL with often reduced penetrance. Predicting leukemia development, therapy response and long term follow up of mutation carriers is challenging because experience from large patient cohorts and their long term follow up are not available. Genetically Engineered Murine Models (GEMMs) represent a promising approach to create individualized and precise models reproducing the molecular makeup of the human disease. This review focuses on PAX5 loss-of-function and summarizes techniques of murine model generation, available GEMMs, which mimic Pax5 loss-of-function in leukemia development and discusses the challenges and drawbacks of these models. These aspects are discussed in the context of creating a robust model, which serves not only for validation of the relevance of a genomic alteration in pB-ALL but at the same time as a valid preclinical model. (C) 2015 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:166 / 172
页数:7
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