4.3 Virus -Induced ALL Animal Models
AKR mice are susceptible to leukemia and murine leukemia viruses(Mulv) have been widely used to simulate human leukemia in susceptible mouse strains(Rein, 2011). In the 1950s, Dr. Charlotte Friend injected the MuLV supernatant from the spleen suspension of leukemia-affected AKR mice into newborn mice to induce leukemia in adult Swiss mice or DBA/2 mice and cause serial transmission(Friend, 1957). Lymphoblastic leukemia and lymphoma caused by retroviral insertion mutations can be used to characterize new genes related to the occurrence of lymphoid leukemia by describing the virus insertion sequence, and confirming misregulation of several Notch signaling genes (Weiser et al., 2007).
Leukemia caused by C-type RNA tumor viruses or retroviruses is mostly T-cell type. If the body’s control system is out of control, this tumor virus can turn hematopoietic cells into leukemic cells under the action of reverse transcriptase, resulting in adult T-cell leukemia. Bovine leukemia virus (BLV) and human T-cell leukemia virus type 1 (HTLV-1) make up a unique retrovirus family. Both viruses cause lymphoproliferative disease, with BLV affecting the B-cell lineage and HTLV-1 affecting the T-cell lineage(Aida, Murakami, Takahashi & Takeshima, 2013). BLV can infect a variety of cell lines(Graves & Ferrer, 1976) and spread to rats(Altanerova, Portetelle, Kettmann & Altaner, 1989), pigs, goats and sheep(Mammerickx, Portetelle & Burny, 1981)artificially. It is estimated that HTLV-1 has infected 5 to 10 million people worldwide and is a causative agent in adult T-cell leukemia/lymphoma (ATLL), as well as other inflammatory diseases(Gallo, Willems & Hasegawa, 2016; Martin, Tagaya & Gallo, 2018; Sodré Barmpas et al., 2019). Researchers injected HTLV-1-infected cell lines into NOG mice intraperitoneally, and other groups were given IR-treated HTLV-1 donor cells. Studies have found that the expression of Tax oncoproteins was up-regulated, and its relationship with Extracellular Vesicles (EVs) had a potential role in continuation of Tax-mediated pathogenesis, and ultimately promoted the development of ALL(Pinto et al., 2019). Tax oncoprotein enhanced uncontrolled replication of T cells and cellular genes (such as IL-2/IL-2R), disrupted DNA repair mechanisms, causes genetic instability, inhibits apoptosis of infected cells, and interferes with cell cycle checkpoints(Ahmadi Ghezeldasht et al., 2013; Currer et al., 2012). In addition, the levels of CD4+and CD8+ T cells in peripheral blood were significantly increased, indicating that HTLV-I infection in peripheral blood may cause the virus to invade CD4+ and CD8+ T cell populations, as well as cells of the monocyte/macrophage cell line(Anderson et al., 2018; Knight, Macatonia, Cruickshank, Rudge & Patterson, 1993). These models are helpful for the identification and function of ALL-associated proto-oncogenes, facilitating us to better understand the mechanisms of virus-induced leukemia, helping to develop new strategies aimed at limiting virus transmission, and playing a huge role in promoting the development of virus-induced leukemia treatment strategies.
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