Leukemia cells are present in the colon in transplantation recipients with CML. (A) Schematic illustrating tet-induced repression of bcr/abl gene expression obtained after crossing ScltTA with bcr/abl mice to produce double-transgenic CML animals. tet binds to the tetracycline-controlled transactivator (tTA), which prevents binding of tTA to the tetracycline response element (TRE) resulting in repression of bcr/abl transcription. In the absence of tet, the tTA is able to bind to the TRE, and there is expression of bcr/abl. (B) Lethally irradiated (1000 cGy) FVB mice were transplanted with TCD B6 BM (10 × 10⁶) and non-TCD BM (10 × 10⁶) cells from CML (SCLTta × BCR/ABL) animals. One cohort was maintained on tet (n = 10), whereas the second was removed from tet after transplantation (n = 8). Mice in both groups were bled 48 to 52 days after transplantation. Peripheral blood was analyzed for total WBC and ANC. Horizontal lines indicate the upper limit of normal for WBC and ANC. (C) Mice in similarly transplanted cohorts (n = 9 or 10/group) were killed 52 to 57 days after BMT, and spleen size and the absolute number of Gr-1⁺ Mac-1⁺ cells were calculated. (D-G) Histology of representative mouse with underlying CML that was killed 83 days after BMT. (D) Granulocytic infiltrate surrounding a central vein in the liver. (E) Granulocytes infiltrating the crypts in the colon (arrows indicate eosinophils). (F) Immature granulocytic precursors within the interstitium of the lung parenchyma (arrow). (G) Perivascular granulocytic infiltrate in the kidney. (H-I) Lethally irradiated FVB mice were transplanted with TCD B6 BM and non-TCD BM cells from CML mice. One cohort was maintained on tet (n = 15), whereas the second group was placed on normal drinking water without tet (n = 12). Mice were killed 50 days after transplantation, and spleen, liver, and colon tissues were obtained from each animal to determine bcr/abl mRNA levels by real-time quantitative PCR. Data are presented as fold increase over c-abl in panel H. The fold increase of bcr/abl over c-abl expression in the spleen, liver, and colon of animals not on tet versus those on tet is shown in panel I. Data are the mean ± SEM. **P < .01. Panels D through G: Images were obtained with an Olympus DP70 digital camera and an Olympus BX45 microscope with a 40×/0.75 NA lens.