In vitro drug response of B-ALL arising from p19^ARF-null HSCs versus pro-B cells. Primary recipients injected with p210BCR/ABL-expressing p19^ARF-null HSC or pro-B cells were killed approximately 2 to 3 weeks after transplantation. EGFP⁺ B-ALL (B220⁺, CD19⁺, IgM⁻) cells were isolated by FACS and cultured in vitro (IMDM + 10% FBS + 55 micromolar 2-ME, no cytokines) for 2 to 3 weeks. Cells were then treated with dexamethasone (A,B) or imatinib mesylate (C,D) at the concentrations indicated, 10⁶ cells per mL. After 48 hours of treatment, half of each sample was stained with PE-conjugated anti–annexin V antibody and 7AAD to evaluate apoptotic response by flow cytometry. Results are presented as percent of survival relative to untreated control (A,C). A small portion of each culture was plated in methycellulose medium (with murine SCF, IL-3, IL-6, Flt3 ligand, and IL-7) to evaluate the clonal potential of residual cells. Results are presented as percent of colonies relative to untreated control (B,D). Significance was determined with Student paired, 1-tailed t test (****P < .001; ***P < .005).