Figure 4.

Reduction in MCL-1 levels only moderately exacerbates haematopoietic cytopenia caused by DNA double-strand break-inducing drugs. Wild-type (wt) and Mcl-1^+/− mice were treated with doxorubicin (2 × 2 mg/kg body weight, i.v.; wild-type n=9; Mcl-1^+/− n=8) or etoposide (1 × 2 mg/kg body weight, i.v.; wild-type n=8; Mcl-1^+/− n=8) and monitored for a total of 28 days. A subset of each cohort was killed 7 days post-treatment for detailed flow cytometric and histological analysis. (a) Lymphocyte and (b) RBC numbers were determined in peripheral blood at the indicated time points post-treatment with doxorubicin (left panel) or etoposide (right panel). Data represent mean ±S.E.M. *P<0.05, **P<0.01, ***P<0.001 (Student's t-test, two tailed, paired, compared with untreated mice). (c) Histological analysis of H&E-stained sections of the bone marrow (sternum) of wild-type and Mcl-1^+/− mice 7 days post-treatment with doxorubicin (upper panel) or etoposide (lower panel). Flow cytometric analysis of the indicated bone marrow (BM) cell populations (d) and the indicated B-cell populations (e) (total cell count for one femur) in wild-type and Mcl-1^+/− mice 7 days post-treatment with doxorubicin (upper panel, wild-type n=3; Mcl-1^+/− n=3) or etoposide (lower panel, wild-type n=3; Mcl-1^+/− n=3) compared with untreated wild-type (n=7) and Mcl-1^+/− mice (n=7). Data represent mean ±S.E.M. *P<0.05 (Student's t-test, two tailed, unpaired, comparing wild-type with Mcl-1^+/− mice). (f) Flow cytometric analysis of total thymic T lymphoid cells in wild-type and Mcl-1^+/− mice 7 days post-treatment with doxorubicin (upper panel, wild-type n=3; Mcl-1^+/− n=3) or etoposide (lower panel, wild-type n=3; Mcl-1^+/− n=3) compared with untreated wild-type (n=7) and Mcl-1^+/− mice (n=7). DN=double negative; DP=double positive; SP=single positive thymocytes. Data represent mean ±S.E.M. P>0.5 (n.s.) (Student's t-test, two tailed, unpaired, comparing wild-type with Mcl-1^+/− mice)