Figure 5. Sos1 deletion abolishes BCR-ABL induced transformation of HSCs in vitro and delays leukemogenesis in vivo.

A. 5-FU enriched BMDCs were retrovirally-infected with pMigBCR-ABL^p210 before being treated with (SOS1^KO) or without (SOS1^fl/fl) tamoxifen and transplanted into lethally irradiated recipient mice. Recipient mice were injected i.p. with tamoxifen or solvent for two days after TX to induce Sos1 deletion and monitored for leukemia induction. Tamoxifen had no effect on cell engraftment or leukemic development (not shown). In addition, it did not affect the efficiency of infection, which was about 20% in the presence or the absence of TX (not shown). Kaplan-Meier plot details the overall survival of transplanted mice (n=6) of 2 independent experiments. P value was determined by Log-rank Test.

B-C. Peripheral blood measurement of mice that received a Sos1 deleted BMDC transplant showed a significantly reduction in leukemic white blood cells (C) gain as well as a reduced leukemic burden (D) of Sos1 deleted BMDCs transplanted mice during the course of disease. Results are from a representative transplantation experiment (n=6) out of two independent ones at the indicated time points. Leukemic burden was measured by the percentage of EGFP positive CD45 cells in the PB. P-values were determined by Students t-test: * p < 0.05; ** p < 0.01; *** p < 0.005.