Figure 2.
Cytokine-dependent activation of a latent leukemic state present in the in vivo progeny of MYC-transduced human CB cells. (A) Survival of secondary (dotted, NRG-3GS, red; NRG, green) recipients transplanted with bulk leukemic cells from primary NRG-3GS recipients (solid red); log-rank test, P < .005. (B) Survival of primary NRG recipients (i, solid green), and secondary NRG and NRG-3GS recipients of matched doses of cells from 2 primary NRG recipients of MYC-transduced cells (ii: NRG-3GS, dotted red; NRG, dotted green); n = 2 experiments, log-rank test, P < .01. (C) Mean ± standard error of the mean chimerism of human cell types within the MYC+GFP+ (solid green) and nontransduced populations (hollow green) detected in the BM of individual NRG recipients of unselected CD34+ or prepurified CD34+38− cells analyzed 30 to 32 weeks after transplant; paired 2-tailed Student t test, n = 4 to 7, grafts initiated from 3 different CB pools. (D) MYC transcripts in bulk GFP+ cells from primary grafts of MYC- or control-transduced cells in NRG-3GS or NRG mice. Grafts were initiated from 3 different CB pools. (E-F) Four-week BM chimerism (E) and phenotype (F) of cells from 3 secondary NRG (green) and NRG-3GS (red) recipients from (Bii); unpaired 2-tailed Student t test. (G) Cytokine concentrations in the supernatants of cytokine-transduced CD34+ CB cells cultured for 6 days. n.d., below the level of detection. (H) Survival of primary NRG recipients of CD34+ cells transduced with cytokines ± MYC cDNAs; log-rank test, P < .05. Experimental design (i) and results (ii).