Genetically Engineered Mouse Models of Human B-cell Precursor Leukemias
Overview
Affiliations
B-cell precursor acute lymphoblastic leukemias (pB-ALLs) are the most frequent type of malignancies of the childhood, and also affect an important proportion of adult patients. In spite of their apparent homogeneity, pB-ALL comprises a group of diseases very different both clinically and pathologically, and with very diverse outcomes as a consequence of their biology, and underlying molecular alterations. Their understanding (as a prerequisite for their cure) will require a sustained multidisciplinary effort from professionals coming from many different fields. Among all the available tools for pB-ALL research, the use of animal models stands, as of today, as the most powerful approach, not only for the understanding of the origin and evolution of the disease, but also for the development of new therapies. In this review we go over the most relevant (historically, technically or biologically) genetically engineered mouse models (GEMMs) of human pB-ALLs that have been generated over the last 20 years. Our final aim is to outline the most relevant guidelines that should be followed to generate an "ideal" animal model that could become a standard for the study of human pB-ALL leukemia, and which could be shared among research groups and drug development companies in order to unify criteria for studies like drug testing, analysis of the influence of environmental risk factors, or studying the role of both low-penetrance mutations and cancer susceptibility alterations.
Challenges and Opportunities for Childhood Cancer Drug Development.
Houghton P, Kurmasheva R Pharmacol Rev. 2019; 71(4):671-697.
PMID: 31558580 PMC: 6768308. DOI: 10.1124/pr.118.016972.
Janke L, Mullighan C, Dang J, Rehg J Vet Pathol. 2019; 56(6):950-958.
PMID: 31170889 PMC: 7140381. DOI: 10.1177/0300985819852138.
Five percent of healthy newborns have an fusion as revealed by DNA-based GIPFEL screening.
Schafer D, Olsen M, Lahnemann D, Stanulla M, Slany R, Schmiegelow K Blood. 2018; 131(7):821-826.
PMID: 29311095 PMC: 5909885. DOI: 10.1182/blood-2017-09-808402.
ZNF423 and ZNF521: EBF1 Antagonists of Potential Relevance in B-Lymphoid Malignancies.
Mesuraca M, Chiarella E, Scicchitano S, Codispoti B, Giordano M, Nappo G Biomed Res Int. 2016; 2015:165238.
PMID: 26788497 PMC: 4695665. DOI: 10.1155/2015/165238.