We studied human and mouse T-ALL using a loss-of-function and IKZF1 re-expression approach, along with primary human T-ALL, and normal human and mouse thymocytes to establish the role of IKAROS and HDAC1 in global regulation of facultative heterochromatin and transcriptional repression in T-ALL. This evidence concerns the gene IKZF1 and acute lymphoblastic leukemia.