Acute lymphoblastic leukemia (ALL) has several sub-types such as pre-B cell, T-cell, and mature B cell which are all characterized by the aggressive proliferation of clonal lymphoblasts. Creative Animodel has contributed carcinogen-induced, viral-induced, transgenic, mosaic, and xenograft as models to the market for a better understanding of AML.
Figure 1: Models of T-cell ALL are caused by Notch-1 activation.
Figure 2: Approaches to induced leukemia
Chemically induced models:
Methylcholanthrene-induced ALL is derived from L5178Y cell line in DBA/2 mice strains. L210 cell line can also be used to generate ALL in preclinical studies. In addition to mice, we also chemically induce pre-B ALL in WKAH/Hkm rats by a nitrosourea derivative, N-Butylnitrosourea (BNU), administered orally 5 days a week for 24 weeks.
AKR/J mice are typical strains of inbred mice to develop T-cell ALL starting at the 5–6 months of age. A recombinant virus, Mink Cell Focus (MCF) is able to accelerate a T cell ALL by targeting thymocytes.
SCID mice are available for the transplantation of human derived ALL cells, which allows engraftment and proliferation in vivo, with extramedullary involvement. We can also generate SCID-beige models with Prkdc mutation on a mouse with BALB/c or CB57/BL/6J background to reduce T and B cells, as well as NK. Besides relevant SCID models, NOD/SCID and NSG models are more efficient as experimental models for ALL to test treatment strategies prior to clinical trial and to explore leucomogenesis. We always keep some obstacles in mind when generating these mice:
● The need to be housed in a pathogen-free environment due to severe immunodeficiency
● The inherited tendency toward spontaneous lymphomas
● The high rate of lethal xenogeneic graft versus host disease with the engraftment of T cells
Genetically engineered models:
Creative Animodel is able to investigate ALL-associated genetic abnormalities in GEMs including BCR-ABL, MML, and ETV-RUNX1 models. Furthermore, there are numerous approaches have been developed to express these proteins in mouse models such as transgenic, knock-in and bone marrow transduction.
There have been other species employed to investigate leukemogenesis or the effectiveness of drugs in ALL.
● An inbred subline of Sprague-Dawley (S/D) rats
● WAG/Rij rat for radiation-induced L4415 leukemia
● In irradiated or non-irradiated guinea pigs to develop Pre-B ALL
● Transgenic zebrafish
Considering the difference between individualized experiments, as well as merits and demerits between different species, Creative Animodel also provides animal model selection services, and is able to help with processing technical problems. We promise unrivalled services and are ready to support with all stages of model creation.