Polycythemia and reticulocytosis induced by JAK2 V617F responds to kinase inhibitor therapy.

<div><p>(A) Hematocrit (left panel) and reticulocyte counts (right panel) of cohorts of mice treated with twice daily oral gavage with 100 mg/kg imatinib (<i>n</i> = 3), 10 mg/kg dasatinib (<i>n</i> = 4), or vehicle (<i>n</i> = 2), determined before initiation of therapy (white bars, “pre”) or after 2 weeks of treatment (black bars, “post”).</p> <p>The hematocrit and reticulocyte count were significantly decreased in response to imatinib therapy (<i>P</i> = 0.0267 and <i>P</i> = 0.0053, respectively, unpaired <i>t</i>-test), while imatinib had no effect on these parameters in normal mice (data not shown).</p> <p>(B) Inhibition of Ba/F3 parental cells grown in IL-3 (green squares) or Ba/F3 cells expressing BCR-ABL (magenta triangles) or JAK2 V617F (red circles) grown without IL-3 by JAK Inhibitor I (left) or AG-490 (right).</p> <p>Note that both JAK Inhibitor I and AG-490 inhibit IL-3-dependent proliferation of parental Ba/F3 cells, but only AG-490 inhibits the growth of BCR-ABL-expressing cells, as previously reported <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000018#pone.0000018-Xie1" target="_blank">[48]</a>.</p> <p>(C) Hematocrit (left panel) and reticulocyte counts (right panel) of mice treated with continuous parenteral administration of 300 µg/day AG-490 (<i>n</i> = 3) or vehicle (<i>n</i> = 2), determined before initiation of therapy (white bars), or after 2 weeks of treatment (black bars).</p> <p>The hematocrit and reticulocyte count were significantly decreased in response to AG-490 therapy (<i>P</i> = 0.0134 and <i>P</i> = 0.0374, respectively, unpaired <i>t</i>-test).</p> <p>There was no significant effect of AG-490 on the hematocrit or reticulocyte count of recipients of JAK2 WT-transduced BM (data not shown).</p>