title: GEMMs addressing Pax5 loss-of-function in childhood pB-ALL.
abstract: 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.
authors.affiliation: Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich-Heine University Dusseldorf, Medical Faculty, Dusseldorf, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Auer
authors.affiliation: Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich-Heine University Dusseldorf, Medical Faculty, Dusseldorf, Germany.
authors.forename: Deborah
authors.initials: D
authors.lastname: Ingenhag
authors.affiliation: Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich-Heine University Dusseldorf, Medical Faculty, Dusseldorf, Germany.
authors.forename: Sanil
authors.initials: S
authors.lastname: Bhatia
authors.affiliation: Institute of Transplantation Diagnostics and Cell Therapeutics (ITZ), Heinrich-Heine University Dusseldorf, Medical Faculty, Dusseldorf, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Enczmann
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC/Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain.
authors.forename: Cesar
authors.initials: C
authors.lastname: Cobaleda
authors.affiliation: Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca, Campus M. de Unamuno s/n, Salamanca, Spain; Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
authors.forename: Isidro
authors.initials: I
authors.lastname: Sanchez-Garcia
authors.affiliation: Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich-Heine University Dusseldorf, Medical Faculty, Dusseldorf, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Borkhardt
authors.affiliation: Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich-Heine University Dusseldorf, Medical Faculty, Dusseldorf, Germany. Electronic address: Julia.Hauer@med.uni-duesseldorf.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Hauer
mesh_terms: D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D018390:Gene Targeting; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D051757:PAX5 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D019683:Penetrance; D010641:Phenotype; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human
keywords: Genetic susceptibility; Leukemia; Murine models; Next generation sequencing; Pax5