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<i>IKZF1</i> encodes the transcription factor IKAROS, a zinc finger DNA-binding protein with a key role in lymphoid lineage development. IKAROS plays a critical role in the development of lineage-restricted mature lymphocytes. Deletions within <i>IKZF1</i> in B-cell acute lymphoblastic leukemia (B-ALL) lead to a loss of normal IKAROS function, conferring leukemic stem cell properties, including self-renewal and subsequent uncontrolled growth. <i>IKZF1</i> deletions are associated with treatment resistance and inferior outcomes. Early identification of <i>IKZF1</i> deletions in B-ALL may inform the intensification of therapy and other potential treatment strategies to improve outcomes in this high-risk leukemia.