6.3 Eμ-Myc transgenic models
Burkitt lymphoma/leukemia is a subtype of ALL, which is characterized by chromosomal translocation leading to Myc gene expression under the control of immunoglobulin heavy chain or light chain promoters. Myc oncogenes are usually highly expressed in human T-ALL(Erikson et al., 1986). Under the control of the IgG heavy chain promoter, the mouse Myc gene produces transgenic mice that mimic the clinically seen t(8;14),most of the mice suffer from B-cell lymphoma/leukemia(Harris, Pinkert, Crawford, Langdon, Brinster & Adams, 1988).
Researchers established three Myc transgenic mouse models. According to the level of Myc, the tumor phenotypes of Myc mice are different, with high expression leading to rapid-onset T-cell lymphoma, low expression leading to late-onset myeloid tumors, and moderate expression levels producing both tumor types(Campbell, Vandenberg, Anstee, Hurlin & Cory, 2017). Later, analyzed the gene expression and function of senescent and non-senescent B-cell lymphomas in Eμ-Myc transgenic mice, researchers found that previously senescent cells in vivo presented a higher tumor initiation potential. It is worth noting that in p53-regulated ALL and AML models, temporary strengthening of senescence can reprogram non-stem bulk leukemia cells into self-renewing, leukemia-initiated stem cells. These findings have far-reaching implications for cancer treatment(Milanovic et al., 2018). Recently, in order to analyze the important role of the microenvironment in regulating human AML population dynamics, researchers investigated the effects of oncogene (c-Myc) and exposure to cytokines such as IL3, GM-CSF and SCF on human AML cells in immunodeficient mice. This finding emphasized the key role these cytokines play in activating normally differentiated human hematopoietic cells(Bulaeva et al., 2020). The leukemia induced by these methods have rapid and powerful reproducibility, which provides a useful and powerful platform for testing and evaluating new treatment medication in human acute leukemia.