Ikzf1, which encodes the transcription factor IKAROS, is a zinc finger DNA-binding protein. It plays a critical role in lymphoid lineage development, being essential for the development of lineage-restricted mature lymphocytes [4]. Ikzf1 is involved in pathways related to lymphocyte differentiation and function, and its normal function is crucial for the proper development and regulation of the immune system. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, can be used to study its functions in vivo.

In multiple myeloma, lenalidomide causes selective ubiquitination and degradation of Ikzf1 by the CRBN-CRL4 ubiquitin ligase, and Ikzf1 is an essential transcription factor in this disease [1]. In pediatric B-cell precursor acute lymphoblastic leukemia (ALL), somatic deletions of Ikzf1 are independently associated with a poor prognosis, and co-occurring deletions with certain genes define a new very-poor prognostic profile named IKZF1plus [2]. In Treg cells, Ikzf1 associates with Foxp3 to repress gene expression, and deletion of its exon 5 in Treg-specific cells leads to IFN-γ overproduction, autoimmune disease, and strong anti-tumor immunity [3]. In B-cell acute lymphoblastic leukemia (B-ALL), deletions within Ikzf1 confer leukemic stem cell properties, treatment resistance, and inferior outcomes [4].

In conclusion, Ikzf1 is vital for lymphoid development and immune system regulation. Studies using KO/CKO mouse models, among other genetic models, have revealed its role in diseases like multiple myeloma, ALL, and autoimmune conditions. Understanding Ikzf1 functions can provide insights into disease mechanisms and potentially new therapeutic strategies for these diseases.