IKZF3

IKZF3 (Aiolos) is a zinc finger transcription factor essential for lymphocyte maturation and transcriptional regulation in hematopoietic cells^[1]. Mechanistically, IKZF3 represses the expression of activating ligands such as MICA and PVR/CD155 in multiple myeloma (MM) cells, acting through direct promoter binding and interaction with IRF4. In disease models, IKZF3 expression influences both tumor progression and immune cell function; high IKZF3 in T-cells correlates with superior overall survival in MM patients treated with immunomodulatory drugs (IMiDs)^[2]. Loss or degradation of IKZF3 by cereblon-targeting agents like lenalidomide and iberdomide modulates IL-2 production and B cell differentiation, highlighting its role in adaptive immunity^[3][4][5]. Compared with IKZF1, IKZF3 exhibits distinct transcriptional targets and is critical for plasmablast differentiation in systemic lupus erythematosus (SLE)^[6][5]. Hotspot mutations in IKZF3 (e.g., L162R) alter DNA binding specificity, hyperactivating B cell receptor signaling and promoting chronic lymphocytic leukemia (CLL), distinguishing its oncogenic potential from other Ikaros family members^[7]. Experimental inhibition of IKZF3 with small molecules, such as the SMO antagonist SANT-1 or natural compounds like baicalein, demonstrates suppressed tumor cell proliferation and altered cell cycle progression, offering translational relevance for therapeutic targeting^[8][9]. Detection of IKZF3 protein using label-free immunosensors enables sensitive monitoring of MM patients under IMiD treatment^[10].