Deletion of Erk1 and Erk2 leads to fatal BM failure and loss of HSC. (A) Kaplan-Meier survival analysis of a cohort of Erk1−/− (n = 23), Mx1-Cre;Erkflox/flox (n = 21), Mx1-Cre Erk1−/−;Erk2flox/flox (n = 22), and littermate control (n = 18) mice following pIpC treatment. Erk1−/−Erk2Δ/Δ mice have a median lifespan of 30 days; control mice remain healthy for >120 days. *P < .05, log-rank test. (B) Hematoxylin and eosin–stained sections from humeri of control, Erk1−/−, Erk2Δ/Δ, and Erk1−/−Erk2Δ/Δ animals 30 days after receiving their last dose of pIpC. (C-D) White blood cell count (WBC) and hematocrit (HCT) of control, Erk1−/−, Erk2Δ/Δ, and Erk1−/−Erk2Δ/Δ mice (*P < .05, ANOVA). (E) Absolute number (mean ± SEM, *P < .05, ANOVA) of LSK, CMP (Lin−Sca1−cKit+CD34+FcγRlo), GMP (Lin−Sca1−cKit+CD34+FcγRhi), MEP (Lin−Sca1−cKit+CD34−FcγR−/lo) of control (n = 6), Erk1−/− (n = 5), Erk2Δ/Δ (n = 5), and Erk1−/−Erk2Δ/Δ mice (n = 6). *P < .05, ANOVA. (F) Absolute number (mean ± SEM, * P < .05, Student t test) of signaling lymphocyte activation molecule (SLAM)-HSC from control (n = 6), Erk1−/− (n = 5), Erk2Δ/Δ (n = 5), and Erk1−/−Erk2Δ/Δ mice (n = 6). *P < .05, ANOVA.