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Farnesyltransferase inhibitor tipifarnib (R115777) preferentially inhibits in vitro autonomous erythropoiesis of polycythemia vera patient cells

Jérôme Larghero, Nathalie Gervais, Bruno Cassinat, Jean-Didier Rain, Marie-Hélène Schlageter, Rose Ann Padua, Christine Chomienne and Philippe Rousselot

Article Figures & Data

Figures

  • Figure 1.

    Dose-dependent effect of tipifarnib on spontaneous BFU-E growth. Peripheral blood mononuclear cells (5 × 105/mL) from patients with PV (▪) were plated for 14 days in the presence of various concentrations of tipifarnib (15 nM to 1.5μM) without addition of EPO in the medium and were BFU-E numbered. Results are given as mean ± SD of triplicate BFU-Es. Controls (▦) are BFU-Es obtained from bone marrow mononuclear cells of healthy donors cultured in the presence of EPO 2 IU/mL and tipifarnib (15 nM to 1.5 μM).

  • Figure 2.

    EPO does not relieve tipifarnib BFU-E growth inhibition. (A) BFU-E colony number in patients with PV (n = 8) at 1.5 μM tipifarnib concentration in the absence or presence of EPO. □ indicates control; ▦, EPO; ▨, tipifarnib; and ▪, EPO + tipifarnib. Pt indicates patient number. (B) Embedded Image indicates dose-dependent BFU-E growth inhibition: ratio of BFU-E colony growth assessed in PV samples between medium alone and tipifarnib-treated samples (n = 8). ▪ indicates EPO rescue of tipifarnib BFU-E growth inhibition: ratio of BFU-E colony growth between EPO- and tipifarnib + EPO–treated samples (n = 8). BFU-E colonies were counted at day 14 with each experiment assessed in triplicate. Error bars indicate 95% confidence intervals.