Functions of the Ikaros transcription factor and the role of IKZF1 gene defects in hematological malignancies

Discovered in the early 1990s, the highly conserved DNA- and protein-binding transcription factor, Ikaros, is now considered one of the most important players in hematopoiesis and the development of certain forms of human malignancies. The Ikaros transcription factor is a multifunctional protein regulating hematopoietic stem cells (HSCs) function, coordinating self-renewal, cell survival processes, cell cycle progression and lymphopoiesis. Ikaros is also considered as one of the most important antileukemic transcription factors. Alterations in the Ikaros gene (IKZF1) characterize a subset of acute lymphoblastic leukemia with significant resistance to treatment and increased risk of relapse. Hematological studies highlight shortened and modified dominant negative (DN) Ik-forms, that play an important role in the development and prognosis of hematological malignances. Currently, extensive research in this field is a priority in the battle against leukemia. This paper describes the structural and functional properties of the Ikaros protein and its family members, important interactions with the nuclear proteins, its influence on gene transcriptional profiles, as well as its considerable involvement in the key hematopoietic processes.