Figure 1.
Deletion of Bcor exons 9 and 10 induces acute T-ALL. (A) Kaplan-Meier survival curves of WT (n = 15), ΔE4 (n = 14), and ΔE9-10 (n = 20) mice after the injection of tamoxifen; data from 2 independent experiments were combined. ***P < .001; *P < .05 by the log-rank test. The causes of death in ΔE9-10 mice are summarized in a table. (B) Flow cytometric profiles of PB, BM, the spleen, and thymus from a representative ΔE9-10 T-ALL mouse. Smear preparation of PB and cytospin preparations of BM, the spleen, and thymus after May-Giemsa staining are depicted below the profiles. Bars represent 10 μm. (C) PB white blood cell (WBC) counts and spleen and thymus weights in moribund ΔE9-10 T-ALL mice and WT and ΔE9-10 mice 12 weeks after the injection of tamoxifen (WBC: WT, n = 15; ΔE9-10, n = 20; ΔE9-10 T-ALL, n = 10; thymus: WT, n = 5; ΔE9-10, n = 5; ΔE9-10 T-ALL, n = 10; spleen: WT, n = 5; ΔE9-10, n = 5; ΔE9-10 T-ALL, n = 10). Bars in scatter diagrams indicate median values. ***P < .001 by the Student t test. (D) A pie graph summarizing the Notch1 status in ΔE9-10 T-ALLs. Genomic data of type 1 deletions and somatic mutations of Notch1 are depicted (n = 8). (E) Nuclear accumulation of cleaved NOTCH1 in the spleen of ΔE9-10 T-ALLs. Formalin-fixed, paraffin-embedded spleens were stained using an anti-NOTCH1 antibody recognizing the cytosolic domain of NOTCH1. Sections were visualized and counterstained with hematoxylin. Bars represent 50 μm.