Negi Vijay, Aplan Peter D
Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Oncoscience. 2022 Oct 24;9:60-63. doi: 10.18632/oncoscience.567. eCollection 2022.
Early/immature T cell precursor acute lymphoblastic leukemia (EITP ALL) represents a subset of human leukemias distinct from other T-ALL, and associated with poor prognosis. Clinical studies have identified chromosomal translocations involving the gene and point mutations of genes as recurrent mutations in patients with EITP-ALL. In a recent study using genetically engineered mice, we demonstrated that cooperation of an mutation with a () fusion gene resulted in EITP-ALL. Highlights of this double transgenic mouse model included the similarity of the immunophenotypic, mutational and gene expression landscape with human EITP-ALL. Additional studies showed that the / are sensitive to selective mutant inhibitors , leading to the possibility that these mice can serve as a useful model for the study of EITP ALL development and therapy.
早期/未成熟T细胞前体急性淋巴细胞白血病(EITP ALL)是人类白血病中的一个子集,与其他T细胞急性淋巴细胞白血病不同,且预后较差。临床研究已确定,涉及该基因的染色体易位和基因的点突变是EITP-ALL患者中的复发性突变。在最近一项使用基因工程小鼠的研究中,我们证明了一个突变与一个()融合基因的协同作用会导致EITP-ALL。这个双转基因小鼠模型的亮点包括其免疫表型、突变和基因表达格局与人类EITP-ALL相似。进一步的研究表明,/对选择性突变抑制剂敏感,这使得这些小鼠有可能成为研究EITP ALL发展和治疗的有用模型。