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Cell Cycle. 2014;13(18):2836-46. doi: 10.4161/15384101.2014.949137.

Genetically engineered mouse models of human B-cell precursor leukemias.

Author information

1
a Department of Pediatric Oncology ; Hematology and Clinical Immunology ; Heinrich-Heine University Dusseldorf ; Medical Faculty ; Dusseldorf , Germany.

Abstract

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.

KEYWORDS:

B-precursor leukemia; BCR-ABL; CLP, common lymphoid progenitor; GEMM, genetically engineered mouse model; LIC, leukemia-initiating cell; MLL; ROS, reactive oxygen species.; TEL-AML1; mouse models; pB-ALL; pB-ALL, preB-Acute lymphoblastic leukemia

PMID:
25486471
PMCID:
PMC4613455
DOI:
10.4161/15384101.2014.949137
[Indexed for MEDLINE]
Free PMC Article

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