RA treatment induces differentiation of leukemic cells and prolongs survival of leukemic mice.

(A) Macroscopic appearance of spleens from 2 mice treated in the same experimental cohort with placebo (upper) or RA for 7 days (lower). (B) Survival curves of mice inoculated with spleen cells from one leukemic mouse (L3). RA treatment was started at day 12 after inoculation, when secondary leukemias were apparent in recipient mice (from analysis of peripheral blood smears). The RA pellet subcutaneously implanted has a duration of approximately 3 weeks. (C) Histologic analysis of leukemic infiltrates in the liver of one leukemic mouse (Ci), and of one leukemic mouse after 7 days of RA treatment (Cii). Original magnification × 400. (D) Extent of leukemic infiltration within the liver of mice treated with placebo (n = 4) or RA (n = 4). For each mouse examined the leukemic cells infiltrating the liver were counted in 40 high-power fields (HPFs; magnification × 630); for each animal the mean number of leukemic cells per HPF was calculated. The columns represent the mean of the values. (E) Differential cell counts in the bone marrow of mice treated with placebo (n = 4) or RA (n = 4). For each examined mouse, 500 myeloid cells were classified according to morphologic features.