IKZF1 alterations in acute lymphoblastic leukemia: The good, the bad and the ugly

Advances in genomics have deepened our understanding of the biology of acute lymphoblastic leukemia (ALL), defined novel molecular leukemia subtypes, discovered new prognostic biomarkers and paved the way to emerging molecularly targeted therapeutic avenues. Since its discovery, IKZF1 has generated significant interest within the leukemia scientific community. IKZF1 plays a critical role in lymphoid development and its alterations cooperate to mediate leukemogenesis. IKZF1 alterations are present in approximately 15% of childhood ALL, rise in prevalence among adults with ALL and become highly enriched within kinase-driven ALL. A cumulating body of literature has highlighted the adverse prognostic impact of IKZF1 alterations in both Philadelphia chromosome (Ph)-negative and Ph-driven ALL. IKZF1 alterations thus emerge as an important prognostic biomarker in ALL. This article aims to provide a state-of-the-art review focusing on the prognostic clinical relevance of IKZF1 alterations in ALL, as well as current and future therapeutic strategies targeting IKZF1-altered ALL.