Assessment of pathway inhibition in situ. Bone marrow mononuclear cells harvested before institution of therapy (day 0) and on day 8 before drug administration were subjected to immunoblotting with antibodies that recognize phosphor-Ser235/236 ribosomal protein S6, GSK3β phosphorylated by Akt on Ser9 and total GSK3β. The shift in HDJ-2 and appearance of prelamin A on day 8 served to confirm FTase inhibition,9,10 whereas Bak served as a loading control. Note that S6 phosphorylation was inhibited in 2 patients (patients A and B) but not the third (patient C).