BCR-ABL expression is indispensable for survival, initiation, and maintenance of Bmi1-expressing CML BC–initiating cells in vivo. (A) Experimental setup. To study leukemia initiation, mice transplanted with B-ALL–initiating cells were fed with (DOX ON) or without (DOX OFF) doxycycline immediately after transplantation. To study leukemia maintenance, recipient mice that had already developed B-ALL under DOX OFF conditions were switched back to a DOX ON diet to stop the further expression of BCR-ABL. (B) Representative image of Scl/p210;Bmi1 mice fed DOX-ON or DOX-OFF diet. (C) Cumulative survival of Scl/p210;Bmi1 mice during leukemia initiation and maintenance DOX-ON or DOX-OFF diets. (P < .05, n = 3-4 mice per group). (D-G) Mice fed with a DOX OFF followed by a DOX ON diet. (D) Representative FACS contour diagram showing EGFP⁺ B-lymphoid progenitors and annexin V⁺ B-lymphoid progenitors present in the peripheral blood of Scl/p210;Bmi1 mice. (E) Frequency of EGFP⁺ B-lymphoid progenitors present in the peripheral blood of Scl/p210;Bmi1 mice (n = 6 mice in each time point). (F) Frequency of annexin V⁺ B-lymphoid progenitors present in the peripheral blood of Scl/p210;Bmi1 mice (n = 6 mice in each time point). (G) Representative FACS contour diagram showing EGFP⁺ B-lymphoid progenitors present in the BM of Scl/p210;Bmi1 mice.