CML-like disease in transplanted mice is reversible and reinducible. Recipients were transplanted with 1 × 10⁶ ufBM cells isolated from noninduced SCLtTA/BCR-ABL (dtg) or noninduced stg donors. Expression of BCR-ABL was induced directly after transplantation for 32 days, reverted for 46 days, and reinduced for 81 days. At each time point, at least 3 dtg and 3 control mice were analyzed. (A) CML-like disease was observed 32 days after transplantation. Average percentages of donor cells (CD45.1⁺), recipient cells (CD45.2⁺), mature granulocytes (Gr-1⁺CD11b⁺), immature granulocytes (Gr-1^lowCD11b⁺), B cells (B220⁺), megakaryocytes (CD41⁺), and erythroid cells (Ter119⁺) are shown (mean ± SD). (B) Histologic analyses of the spleen show infiltration of granulocytes and disturbed follicles in recipients transplanted with dtg, but not control BM. Slides are depicted with an original magnification of ×20. (C) After reversion of BCR-ABL expression for 46 days, CML-like disease was undetectable in the BM or spleen of all recipients. (D) Histologic analyses of spleens showed no alterations of spleen morphology in reverted animals. (E) Reappearance of disease was evident by increasing percentages of dtg donor cells (CD45.1⁺) and increases in the percentage of immature granulocytes, 81 days after reinduction. (F) Infiltration of granulocytes into the spleen of reinduced recipients of dtg BM was evident by NACE staining and is shown at original magnification ×20. (G) Percentage of Gr-1⁺/CD11b⁺cells in the PB of mice that had been induced for 32 days, reverted for 56 days, and reinduced for 81 days showing neutrophilia is dependent on BCR-ABL activity. (H) Splenomegaly was observed on reinduction of BCR-ABL expression. (I) Relative expression of BCR-ABL was analyzed by quantitative reverse-transcribed polymerase chain reaction and was assessed in relation to glyceraldehyde-3-phosphate dehydrogenase in BM and spleen of induced, reverted, and reinduced mice. *P < .05.