Reversible Ikaros knockdown promotes BCR-ABL1⁺ B cell leukemogenesis. (A) Kaplan-Meier survival analysis of BCR-ABL1^P190;Vav-tTA;TRE-GFP-shIkaros mice (n = 19) and BCR-ABL1^P190;Vav-tTA control mice (n = 17). Median survival 36 d versus 80 d, respectively; P < 0.0001, Log-rank (Mantel-Cox) test. (B) Flow cytometry of CD19/IgM and CD24/CD43 immunophenotype of splenocytes isolated from representative primary leukemic mice, and GFP expression of CD19⁺IgM^– cells. (C) Schematic of adoptive transfer approach to generate BCR/ABL1⁺ B-ALL accelerated by reversible Ikaros knockdown. TRE-GFP-shIkaros or TRE-GFP-shRenilla transgenic bone marrow cells are co-transduced with MSCV vectors expressing BCR/ABL1 and tTA, and transplanted into lethally irradiated recipient mice. (D) Kaplan-Meier survival analysis of mice transplanted with TRE-GFP-shIkaros (n = 17) or control TRE-GFP-shRenilla (n = 16) cells infected as in C. Median survival 17 d versus 22 d, respectively; P < 0.0001, log-rank test. (E) Flow cytometry of CD19, IgM, and GFP expression of splenocytes isolated from representative leukemic primary recipient mice transplanted with infected TRE-GFP-shIkaros transgenic bone marrow cells.