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. 2020 Jan 24;135(13):1019–1031. doi: 10.1182/blood.2019003014

Figure 6.

Figure 6.

Bim heterozygosity rescues B lymphopoiesis, reduces apoptosis, and accelerates lymphomagenesis in MNT-deficient Eμ-Myc mice. (A) BIM and MCL-1 expression is elevated in MNT-deficient CD19+ cells. Cells were fluorescence-activated cell sorted from spleens of 4-week-old mice. (B-C) Bim heterozygosity largely restores B lymphopoiesis in young Mntfl/fl Rag1Cre mice. Flow cytometric enumeration of B lymphoid cells in bone marrow (B) and spleen (C) of 6-week-old mice. Data include mice in Figure 4 plus additional mice. Bar graphs show mean ± SD; *P ≤ .05; **P ≤ .01; ****P ≤ .0001. (D-E) Bim heterozygosity partially restores B lymphopoiesis in young MNT-deficient Eμ-Myc mice. Enumeration of B lymphoid cell populations in (D) bone marrow and (E) spleen of the indicated genotypes. Data for controls include certain mice in Figure 1C-D. Mean ± SD; *P ≤ .05; **P ≤ .01; ****P ≤ .001; ****P ≤ .0001. (F) Bim heterozygosity ameliorates enhanced apoptosis of pro-B and pre-B cells in the bone marrow of young MNT-deficient Eμ-Myc mice. Data include mice from Fig. 1C. Mean ± SD; *P ≤ .05; ns = not significant. (G) Bim heterozygosity accelerates lymphomagenesis in MNT-deficient Eμ-Myc mice. Kaplan-Meier survival curves showing enhanced morbidity of Bim+/− Mntfl/fl Eμ-Myc/Rag1Cre (orange) mice compared with Mntfl/fl Eμ-Myc/Rag1Cre (blue) mice, and of Bim+/− Mntfl/+ Eμ-Myc/Rag1Cre (mustard) mice compared with Mntfl/+ Eμ-Myc/Rag1Cre (lime green) mice. Survival curves for Eμ-Myc/Rag1Cre, Mntfl/+ Eμ-Myc/Rag1Cre, and Mntfl/fl Eμ-Myc/Rag1Cre mice are those shown in Figure 1A. Log-rank test; *P ≤ .05; ****P ≤ .0001.