Age-related hematopoietic defects alter the leukemogenic potential of LSCs. (A) Secondary recipients of splenocytes from leukemic mice grafted with young BM^BCR-ABL cells developed MPDs and B-lymphoid leukemia. Splenocytes (5 × 10⁶) from primary young BM^BCR-ABL recipients were transplanted into secondary recipients (n=15). (B) Secondary recipients of 5 × 10⁶ splenocytes from leukemic mice grafted with old BM^BCR-ABL cells (n=12) developed MPDs with no significant involvement of B-lineage cells. (C) The frequency of total leukemic GFP⁺ cells and leukemic myeloid GFP⁺ Gr-1⁺CD11b⁺ cells in the spleens of secondary recipients of splenocytes from tumors derived from young BM^BCR-ABL cells was increased compared with secondary recipients of tumors derived from old BM^BCR-ABL cells. (D) The frequency of B-lineage cells in the spleen of secondary recipients of tumors derived from young BM^BCR-ABL cells was decreased compared with secondary recipients of tumors derived from old BM^BCR-ABL cells. In all transfers, donor splenocytes were transplanted into at least 3 secondary recipients. At least 3 primary recipients were analyzed in each experiment. Cell frequency shown in C-D is presented as the mean frequency of cells plus or minus SEM. The mice analyzed for C-D developed MPDs with no B-lineage involvement.