Figure 6: A. Knockdown of p38 reverses dasatinib-mediated suppression of leukemic progenitor. BCR/ABL expressing, KT-1 cells were transfected with control siRNA or p38 siRNA and subsequently incubated in methylcellulose, in the presence or absence of dasatinib (1 nM), and leukemic progenitor colony formation was assessed. Data are expressed as percent control colony formation of untreated samples for each condition and represent means ± S.E. of 3 independent experiments (p=0.0185).
Figure 6: B. Dasatinib inhibits the growth of leukemic myeloid progenitors from CML patients in a p38 MAP kinase-dependent manner. Peripheral blood or bone marrow mononuclear cells from newly diagnosed CML patients were plated in methylcellulose culture assay system with 10nM of dasatinib in the presence or absence of SB203580 as indicated. CML patient derived CFU-GM progenitor colonies were scored on day 14 of culture.
The data are expressed as percent control of CFU-GM colony numbers for untreated cells. Each patient experiment was repeated 1–5 times. A mean of all experiments is presented in the figure. (paired t-test, dasatinib vs. dasatinib +SB203, p=0.007)