B-lymphoid leukemogenic potential declines in parallel with age-related declines in B lymphopoiesis. (A) Immunostaining used to define pre-pro-B cells (Lin⁻ CD19⁻CD45R⁺AA4.1⁺) and pro/pre-B cells (Lin⁻ CD19⁺CD45R⁺AA4.1⁺) in murine BM. (B) The frequency of lymphoid progenitor populations in the BM progressively declined in mice of increasing age. Groups of young (5- to 7-week-old; n=4), middle-aged (42- to 44-week-old; n=2), and old (90- to 104-week-old; n=3) mice were analyzed. Steady-state frequencies are presented as the mean plus or minus SEM. 5-FU frequencies are presented from the pooled BM of 4 young, 7 middle-aged, and 4 old mice. Total B-lineage cells represents CD19⁺CD45R⁺ cells. Pre-pro-B-cell frequencies were 0.103% in young, 0.073% in middle-aged, and 0.01% in old 5-FU–treated mice, respectively. (C) The incidence of B-lymphoid leukemia in Rag1^−/− recipients of BM^BCR-ABL cells was reduced with increasing BM age. Recipients of middle-aged (n=8) BM^BCR-ABL cells developed B-lymphoid leukemia less frequently than recipients of young (n=8) BM^BCR-ABL cells but more frequently than recipients of old (n=7) BM^BCR-ABL cells. The recipients of young and old BM^BCR-ABL are the same as those shown in Figure 1F.