ERK inhibition reduces CFU-M, whereas SHP2 inhibition reduces CFU-G. (A) Marrow mononuclear cells obtained from mice not exposed to 5-FU were cultured in methylcellulose with IL-3, IL-6, and SCF at 10 000 cells/mL, with either no inhibitor, 5 μM U0126, or 5 μM PD98059. CFUs were enumerated 8 days later. Control cultures yielded on average 67 CFU-G, 67 CFU-M, and 55 CFU-GM per 30 000 cells cultured. The percentage of each CFU obtained with the 2 MEK inhibitors relative to the control colony numbers is shown (mean and SE from 3 experiments). *P < .001 comparing CFU obtained with versus without inhibitor (Student t test). (B) Marrow mononuclear cells were cultured similarly in methylcellulose with either no chemicals, TPA alone, or TPA with U0126. Control cultures yielded on average 151 CFU-G, 129 CFU-M, and 132 CFU-GM per 30 000 cells cultured. The percentage of each CFU obtained with 100 nM TPA or TPA combined with the ERK inhibitor relative to the control is shown (mean and SE from 3 experiments). *P < .001 comparing CFU obtained with versus without TPA; #P < .01 comparing CFU obtained with TPA with versus without U0126. (C) Marrow mononuclear cells were cultured with no inhibitor or 50 μM NSC-87877. Control cultures yielded on average 67 CFU-G, 67 CFU-M, and 55 CFU-GM per 30 000 cells cultured. The percentage of each CFU obtained with the SHP2 inhibitor relative to the control is shown (mean and SE from 3 experiments). *P < .01 comparing CFU obtained with versus without inhibitor.