Ikzf2-flox Mouse

Ikzf2, also known as Helios, is a transcription factor belonging to the Ikaros family. It plays a crucial role in maintaining the function and stability of regulatory T (Treg) cells, and is involved in multiple biological processes such as T-follicular helper, NK-and T-regulatory cell physiology [1,4]. It may also participate in regulating the development of ICOS+ Th cells to mediate immune response in the spleen of Schistosoma japonicum-infected mice [6].

In animal models, IKZF2 deficiency reduces tumor growth in mice, indicating its potential role in tumor-immune evasion. Specifically, in myeloid leukemia, IKZF2 is highly expressed in leukemic stem cells (LSCs), and its depletion in acute myeloid leukemia (AML) cells reduces colony formation, increases differentiation and apoptosis, and delays leukemogenesis. IKZF2 regulates a HOXA9 self-renewal gene expression program and inhibits a C/EBP-driven differentiation program in MLL-AF9 LSCs [5]. Dual degraders of IKZF2 and casein kinase 1α (CK1α) like DEG-35 and DEG-77 can delay leukemia progression in murine and human AML mouse models by blocking cell growth and inducing myeloid differentiation [2,3]. Also, treatment with the selective IKZF2 glue degrader NVP-DKY709 delays tumor growth in mice with a humanized immune system and enhances immunization responses in cynomolgus monkeys [1].

In conclusion, Ikzf2 is essential for the function and stability of Treg cells and has a significant impact on tumor growth and leukemia development. The study of Ikzf2 knockout or conditional knockout mouse models has provided valuable insights into its role in cancer immunotherapy and leukemia treatment, highlighting its potential as a therapeutic target in these disease areas.