Figure 3.
SLIT2 knockdown induces APL clonal expansion and reduces overall survival in vivo. Overview of the mouse model for APL generation. (A) Schematic representation of the generation of the isogeneic mouse model for APL engraftment using blasts from the hCG-PMLRARA mice (CD45.2) transplanted in Pepboy mice (CD45.1). (B) The probability of overall survival in mice transplanted with murine APL blasts transduced with shSlit2 and scrambled as a control (shCTRL). Survival curves were estimated using the Kaplan–Meier method and the log-rank test was used for comparison. (C) Weekly bleedings of mice were used to determine the leukocyte count (*109/L) and monitor disease progression. At sacrifice, APL blasts and cells from Pepboy mice were analyzed by flow cytometry using markers against CD117, Gr1, CD16/32, and CD34, as indicated (inside the population CD45.2+ and lineage negative). Scatter plots showing engraftment of donor APL blast cells (D) in bone marrow (BM), (E) spleen (percentual of engraftment and spleen weight), and (F) peripheral blood (PB) of transplanted mice at sacrifice. Data were expressed as median values. *** indicates p < 0.001; n.s. indicates not significant.