In addition to driving B-lymphoid development, Ikaros has been reported to repress hematopoietic stem-cell specific gene-expression programs during early lineage specification, a function not shared with the other two major regulators of B-cell development that are found mutated in Ph+ ALL, PAX5, and EBF1 (Figure 4) (105, 116, 128). Here, IKZF1 is linked to acute lymphoblastic leukemia.