Ikaros family zinc finger protein 1 and Ikaros family zinc finger protein 3 (IKZF1 (Ikaros), IKZF3 (Aiolos))

IKZF1 (Ikaros family zinc finger protein 1) and IKZF3 (Ikaros family zinc finger protein 3, also known as Aiolos) are members of the Ikaros family of zinc finger transcription factors, which regulate gene expression crucial for the development, differentiation, and function of lymphoid and other hematopoietic cells[1][4][6][9][10]. They bind DNA through C2H2-type zinc finger motifs and function as homo- or heterodimers with each other and with other family members. Both are key regulators of B-cell and T-cell development and function, chromatin remodeling, and immune system maintenance. Frequent alterations or deletions in these genes are associated with lymphoid malignancies, particularly B-cell acute lymphoblastic leukemia and multiple myeloma[2][4]. They are therapeutically targeted by immunomodulatory drugs (IMiDs) such as lenalidomide and pomalidomide, which induce their proteasomal degradation via the cereblon E3 ubiquitin ligase, leading to anti-tumor activity especially in multiple myeloma. Their status serves as a prognostic and predictive biomarker in various hematological diseases, but targeting increases the risk of infection and immune dysfunction[2][4][5].

Other names

Ikaros (IKZF1)Aiolos (IKZF3)IkZF familyDNA-binding protein Ikaros

Targeted protein degradation via cereblon-dependent ubiquitination/proteasomal degradation (IMiDs such as lenalidomide/pomalidomide promote cereblon-mediated IKZF1/IKZF3 degradation) Inhibition of transcriptional regulatory function, leading to anti-cancer (notably anti-myeloma) effects