![FBXO11 deletion accelerates lymphomagenesis in Eμ-myc–transgenic mice. (A) Kaplan-Meier survival analysis of Eμ-myc (n = 33), Eμ-myc/FBXO11fl/fl;CD19-Cretg/+ (KO) (n = 21) and Eμ-myc/FBXO11fl/+;CD19-Cretg/+ (HET) (n = 16) mice, with a median survival time of 121, 89, and 85 days, respectively. Eμ-myc (n = 33) are a combination of Eμ-myc/FBXO11fl/fl (n = 23) and Eμ-myc/FBXO11fl/+ (n = 10). P < .0001 log-rank (Mantel-Cox) test. (B) B220 and IgM expression in lymphomas from Eμ-myc (n = 17), Eμ-myc/FBXO11fl/fl;CD19-Cretg/+ (KO) (n = 16), and Eμ-myc/FBXO11fl/+;CD19-Cretg/+ (HET) (n = 9) mice. (C) B220 and IgD expression in lymphomas from Eμ-myc (n = 16), Eμ-myc/FBXO11fl/fl;CD19-Cretg/+ (KO) (n = 10), and Eμ-myc/FBXO11fl/+;CD19-Cretg/+ (HET) (n = 5) mice. (D) Representative flow cytometry of B220 and IgM expression in lymphoma from Eμ-myc, Eμ-myc/FBXO11-KO, and Eμ-myc/FBXO11 HET mice. (E) Representative H&E stains (top row) and immunohistochemistry for cleaved caspase 3 (middle row) and Ki-67 (bottom row) performed on Eμ-myc primary lymphoma with the indicated genotypes (original magnification ×200). Scale bars, 50 μm. Insets show high-magnification images. (F) Quantification of macrophages in Eμ-myc lymphoma with the indicated genotypes (n = 6 mice for each genotype). Data are mean (± standard deviation [SD]) macrophages per 40× field. Quantification of cleaved caspase 3+ (G) and Ki-67+ (H) cells in Eμ-myc lymphoma with the indicated genotypes (n = 4 mice for each genotype). Data are mean ± SD. (I) BCL6 stability in Eμ-myc/FBXO11-KO lymphoma cells. Western blot showing BCL6 protein expression after treatment with CHX for the indicated times in 3 immortalized Eμ-myc/FBXO11fl/fl lymphoma cell lines transduced with a tamoxifen-inducible CreERT2 vector. Cre recombinase was activated by treatment with 10 nM 4-hydroxytamoxifen (4-OHT) for 4 hours to induce deletion of the FBXO11 floxed gene. A20 is a mouse BCL6+ B lymphoma cell line used as control. **P < .01, ***P < .001, unpaired 2-tailed Student t test.](https://ash.silverchair-cdn.com/ash/content_public/journal/bloodadvances/5/23/10.1182_bloodadvances.2021005682/3/advancesadv2021005682f3.png?Expires=1724926301&Signature=CTBKyunGN9xf0sIZMVV3UecBSMLcCKZU98VbKVyvPY7y9cvh54AngrhpXfY4i8ssSZTITxfP1JYraoS6dLlIUmfyWnFV5~zgTpGnU0KWbLPYH~KKfccr6YlSbK1-a~m4Rn9z3pQuw~h7GzrAUTyTyrgT-Ep9Xlfo9-tf0G~WnhRJgUhB1X133N8aPgzUt2EsWKwmLRZ7q2DCsNFJq~sKHea3r19PPTXPJYFm2L6dTf1J-oKBjImQvBF0FFMMq7YupushoFln3wqQThdEppkxkeww1aORqFWii4zQgVRytZiXgeEILR~O001YE9KVvYZ53YX65YDwTQkd4Hr88rdtow__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
FBXO11 deletion accelerates lymphomagenesis in Eμ-myc–transgenic mice. (A) Kaplan-Meier survival analysis of Eμ-myc (n = 33), Eμ-myc/FBXO11fl/fl;CD19-Cretg/+ (KO) (n = 21) and Eμ-myc/FBXO11fl/+;CD19-Cretg/+ (HET) (n = 16) mice, with a median survival time of 121, 89, and 85 days, respectively. Eμ-myc (n = 33) are a combination of Eμ-myc/FBXO11fl/fl (n = 23) and Eμ-myc/FBXO11fl/+ (n = 10). P < .0001 log-rank (Mantel-Cox) test. (B) B220 and IgM expression in lymphomas from Eμ-myc (n = 17), Eμ-myc/FBXO11fl/fl;CD19-Cretg/+ (KO) (n = 16), and Eμ-myc/FBXO11fl/+;CD19-Cretg/+ (HET) (n = 9) mice. (C) B220 and IgD expression in lymphomas from Eμ-myc (n = 16), Eμ-myc/FBXO11fl/fl;CD19-Cretg/+ (KO) (n = 10), and Eμ-myc/FBXO11fl/+;CD19-Cretg/+ (HET) (n = 5) mice. (D) Representative flow cytometry of B220 and IgM expression in lymphoma from Eμ-myc, Eμ-myc/FBXO11-KO, and Eμ-myc/FBXO11 HET mice. (E) Representative H&E stains (top row) and immunohistochemistry for cleaved caspase 3 (middle row) and Ki-67 (bottom row) performed on Eμ-myc primary lymphoma with the indicated genotypes (original magnification ×200). Scale bars, 50 μm. Insets show high-magnification images. (F) Quantification of macrophages in Eμ-myc lymphoma with the indicated genotypes (n = 6 mice for each genotype). Data are mean (± standard deviation [SD]) macrophages per 40× field. Quantification of cleaved caspase 3+ (G) and Ki-67+ (H) cells in Eμ-myc lymphoma with the indicated genotypes (n = 4 mice for each genotype). Data are mean ± SD. (I) BCL6 stability in Eμ-myc/FBXO11-KO lymphoma cells. Western blot showing BCL6 protein expression after treatment with CHX for the indicated times in 3 immortalized Eμ-myc/FBXO11fl/fl lymphoma cell lines transduced with a tamoxifen-inducible CreERT2 vector. Cre recombinase was activated by treatment with 10 nM 4-hydroxytamoxifen (4-OHT) for 4 hours to induce deletion of the FBXO11 floxed gene. A20 is a mouse BCL6+ B lymphoma cell line used as control. **P < .01, ***P < .001, unpaired 2-tailed Student t test.