Figure 3.
Androgen signaling induces increased susceptibility to AML in male recipients. (A-B) The measurement of serum testosterone level in (A) healthy WT male (n = 3) and female (n = 5) mice and (B) WT male (n = 6) and female (n = 5) recipients transplanted with 1° high AR–expressing AML donor cells at the end point. (C) Measurement of the serum DHT level in WT male recipients transplanted with low AR–expressing AML donor cells in the absence or presence of in vivo finasteride treatment and WT female recipients transplanted with low AR–expressing AML donor cells at the end point (n = 3-5). (D) Viability of purified 1° low AR–expressing AML cells treated with DHT (0, 10, 100, 250 pg/mL; n = 4) in the absence or presence of 150 nM ARN509 for 24 hours. (E) Secondary transplantation was done retro-orbitally with 1° CD45.1 low AR–expressing AML donor cells to CD45.2 WT male recipients; at 1 week after transplantation, the mice were administered 50 mg/kg finasteride daily intraperitoneally for a week. Mice were euthanized at 4 weeks after transplantation; the blood, bone marrow, and spleen were sampled (n = 3-5 in each group). (F) CBC analysis of recipient mice in panel E at the end point. (G) Progression of the peripheral WBC numbers in recipient mice in panel E after transplantation. (H) Spleen weights (milligram) of recipient mice in panel E at the end point. (I-J) Counts of AML cells in the Lin- population in the bone marrow (I) and spleen (J) of recipient mice in panel E at the end point. (K-L) Counts of LICs in the bone marrow (K) and spleen (L) of recipient mice in panel E at the end point. (M) Scheme showing male recipients transplanted with low AR–expressing AML cells and that subsequently received in vivo intraperitoneal treatment of finasteride (20 mg/kg per day) for 2 or 4 weeks. (N) Kaplan-Meier curve used to estimate the survival benefit of in vivo finasteride treatment; ∗P < .05; ∗∗P < .01, as determined using a log-rank test. Panels A-C, F, H-L, error bars represent the mean ± SEM of replicates. ∗P < .05; ∗∗P < .01, as determined using a 1-tailed unpaired Student t test. Panels D,G, error bars represent the mean ± SEM of replicates. ∗∗P < .01, as determined using a 1-way ANOVA test. BA, basophil; Ctl, control; EO, eosinophil; LY, lymphocyte; MO, monocyte; NE, neutrophil; PBS, phosphate-buffered saline.

Androgen signaling induces increased susceptibility to AML in male recipients. (A-B) The measurement of serum testosterone level in (A) healthy WT male (n = 3) and female (n = 5) mice and (B) WT male (n = 6) and female (n = 5) recipients transplanted with 1° high AR–expressing AML donor cells at the end point. (C) Measurement of the serum DHT level in WT male recipients transplanted with low AR–expressing AML donor cells in the absence or presence of in vivo finasteride treatment and WT female recipients transplanted with low AR–expressing AML donor cells at the end point (n = 3-5). (D) Viability of purified 1° low AR–expressing AML cells treated with DHT (0, 10, 100, 250 pg/mL; n = 4) in the absence or presence of 150 nM ARN509 for 24 hours. (E) Secondary transplantation was done retro-orbitally with 1° CD45.1 low AR–expressing AML donor cells to CD45.2 WT male recipients; at 1 week after transplantation, the mice were administered 50 mg/kg finasteride daily intraperitoneally for a week. Mice were euthanized at 4 weeks after transplantation; the blood, bone marrow, and spleen were sampled (n = 3-5 in each group). (F) CBC analysis of recipient mice in panel E at the end point. (G) Progression of the peripheral WBC numbers in recipient mice in panel E after transplantation. (H) Spleen weights (milligram) of recipient mice in panel E at the end point. (I-J) Counts of AML cells in the Lin- population in the bone marrow (I) and spleen (J) of recipient mice in panel E at the end point. (K-L) Counts of LICs in the bone marrow (K) and spleen (L) of recipient mice in panel E at the end point. (M) Scheme showing male recipients transplanted with low AR–expressing AML cells and that subsequently received in vivo intraperitoneal treatment of finasteride (20 mg/kg per day) for 2 or 4 weeks. (N) Kaplan-Meier curve used to estimate the survival benefit of in vivo finasteride treatment; ∗P < .05; ∗∗P < .01, as determined using a log-rank test. Panels A-C, F, H-L, error bars represent the mean ± SEM of replicates. ∗P < .05; ∗∗P < .01, as determined using a 1-tailed unpaired Student t test. Panels D,G, error bars represent the mean ± SEM of replicates. ∗∗P < .01, as determined using a 1-way ANOVA test. BA, basophil; Ctl, control; EO, eosinophil; LY, lymphocyte; MO, monocyte; NE, neutrophil; PBS, phosphate-buffered saline.

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