Deletion of ME results in failure of MLL-AF9 leukemic cells to transplant into syngeneic sublethally irradiated recipient mice. (A) Diagram depicts experimental procedures. (B-D) Shown are CBC data from weeks 0 to 4 posttransplant for recipients of MEfl4/m1 cells, with and without pretreatment with 4-OH TAM; extent of normal values indicated by grayed zone. Mice receiving cells with no 4-OH TAM pretreatment became frankly leukemic, anemic, and thrombocytopenic over the 4 weeks of monitoring. At week 4, most recipients of the untreated cells were moribund, and the mice were necropsied. Error bars depict standard deviation. Statistical significance (Student t test) was observed at week 4 for leukocytes and platelets (P < .05). (E-H) Deletion of ME results in failure of leukemic cells to significantly infiltrate organs of irradiated recipients. Mice receiving 4-OH TAM–pretreated MLL-AF9 leukemia cells maintained normal spleen weights (E-F), as well as livers and bone marrow essentially devoid of infiltrating leukemia; non-pretreated cells infiltrated spleen, liver, and bone marrow (G-H). (E) Gross photographs of spleens from mice injected with untreated and 4-OH TAM–pretreated cells. (F) Scattergrams of spleen weights of the 4 experimental groups, as indicated; number of spleens in cohort in parentheses. Average is demarcated by horizontal bar; P value determined by Student t test. (G-H) Photomicrographs of liver (G) and bone marrow (H), showing extensive infiltration by leukemic cells (original magnification ×200 magnification; hematoxylin and eosin staining).
