Figure 7.
Inhibition of signaling downstream of FLT3, especially of STAT5, appears critical to achieving a cytotoxic response to lestaurtinib and PKC412. Western blot images showing the in vitro effects of lestaurtinib and PKC412 on FLT3 phosphorylation and phosphorylation of the downstream signaling proteins STAT5, AKT, and MAP kinase in MNCs following 1-hour exposure to a range of concentrations of each drug. Three of the 5 cases (M-6, M-7, and W-3) were in vitro cytotoxic responders to lestaurtinib, while 2 of the 5 cases (M-7 and W-3) were responsive to PKC412. MTS assay-derived cytotoxic IC50 concentrations for case-by-case comparison are shown in Table 2.