Fig. 4.
p53 and targeted therapy in murine CML. (a) Representative immunohistochemical stains to assess p53 expression in the spleens of healthy vs. leukemic mice treated as indicated. (b) Fluorescence imaging of a cohort of p53+/+ and p53−/− leukemia-bearing mice killed at various times after imatinib treatment. Representative examples are shown. (c) Kaplan–Meier plot detailing survival times of leukemic mice grouped by genotype upon imatinib treatment; imatinib was started at the onset of leukemia (day 0), and a green bar indicates the treatment interval. Leukemias are derived from BCR-ABL-transduced p53+/+ HSCs (black, n = 15), p53+/− HSCs (blue, n = 24), or p53−/− (red, n = 10); P = 0.0002 (p53+/+ vs. p53+/−); P < 0.0001 (p53+/+ vs. p53−/−); P = 0.08 (p53+/− vs. p53−/−). (d) Bone marrow lysates of p53+/+ (+) or p53−/− (−) leukemias were prepared from untreated animals (Untr) or at various times after a single treatment with imatinib and subjected to immunoblotting with antibodies against phosphorylated and total p56 (P-p56, p56) and tubulin (tub).