sCFU-E cells are expanded in human PV, and inhibition of IGF1R/IRS2 signaling suppresses Epo-hypersensitive erythroid colonies. (A) Percentages of CD34⁺CD36⁺ and CD34^–CD36⁺cells increase in PV samples. (B) In vitro culture of sorted BFU-E cells from PV or controls. Cells are examined by flow cytometry on indicated day after culture. (C) Inhibitors of IRS2 or IGF1R kinase activity reduce sorted murine sCFU-E growth in vitro. Data presented are 48 hours in culture. (D) IRS2 and IGF1R kinase inhibitors reduce the number of erythroid colonies grown from peripheral mononuclear cells from patients with PV. Cells are cultured in methylcellulose media with SCF (50 ng/mL) and low Epo (0.05 U/mL), and colonies are scored on day 14. (E) Current model of EpoR-IGF1R/IRS2 signaling cross talk. inh., inhibitor .∗P < .05; ∗∗P < .01, Student’s t test or 1-way ANOVA.