FIGURE 5.

Notch1 mutations target CD8⁺ T-cells that contain leukemogenic activity. Recipient mice transplanted with Kras G12D cells were killed at a moribund stage. A, evaluation of the Notch1 type 1 deletion in thymocytes (Thy) and purified bone marrow myeloid cells (Mye) of moribund mice with both T-ALL and myeloproliferative neoplasm. B, recipient mice transplanted with Kras G12D cells were killed at the pre-leukemia stage (8 weeks after transplantation) or at a moribund stage. Thymocytes (1 × 10⁵) were further transplanted into sublethally irradiated secondary recipient mice. Kaplan-Meier survival curves are plotted against days after transplantation. The p value was determined by the log-rank test. C, HSCs expressing KRAS G12D were sorted and transplanted into primary recipient mice (1st). Subsequently, 1 × 10⁶ T-ALL cells were transplanted into sublethally irradiated recipient mice (2nd–5th). Black lines represent the average survival of T-ALL mice. D, limiting dilution analysis of the frequency of T-LICs. Sublethally irradiated CD45.1 recipient mice were transplanted with various numbers of T-ALL cells. The percentage of recipient mice free of T-ALL for up to 20 weeks post-transplant is plotted. The frequency of T-LICs was calculated using L-Calc software.