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Since binding and clearance of TPO require ongoing platelet production, TPO levels may serve as a surrogate marker for megakaryopoiesis. Although prior published studies of TPO-receptor agonists sometimes collected TPO levels, the data were not analyzed to determine whether the extent of TPO elevation was related to response [25, 26]. As previously observed [7, 9], TPO levels in our http://www.selleck.cn/products/Staurosporine.html study did not differ with the chronicity of ITP or with receipt of concurrent therapy specific for ITP. Moreover, among patients with ITP, TPO levels only modestly decreased with increasing platelet count due to treatment. These data do not exclude the possibility that a transient increase in TPO levels might occur with acute onset on ITP. However, we observed that high TPO levels were associated with a lack of a durable response to treatment with a TPO receptor agonist. Of the 24 evaluable patients who had been or were being treated with a TPO receptor agonist at the time of study participation, http://www.selleckchem.com/products/epz-5676.html eight of the nine non-responders had a serum TPO level >95 pg/mL. This association remained significant when the analysis was limited to the 21 evaluable patients who were being treated for ITP. These data suggest that TPO levels may have clinical utility in prospectively predicting a durable response to TPO receptor agonists among ITP patients offered this therapy. This study is limited by its small size and carries with it all the caveats of a retrospective analysis. Our observation that elevated TPO levels predict http://www.selleckchem.com/products/ly2109761.html lack of response to TPO agonists is unlikely to be confounded by patient treatment because resolution of thrombocytopenia decreased rather than increased TPO levels. Our findings support the need for larger prospective studies to confirm the central observations made herein: (1) that TPO levels have diagnostic utility in differentiating hypoproliferative from consumptive thrombocytopenia; and (2) that TPO levels may predict clinical response to TPO receptor agonists. The observation that some patients reported to have ITP have elevated TPO levels suggests two possibilities: that some ITP patients have such severe reduction in megakaryopoiesis that even TPO receptor agonist treatment cannot overcome the defect, or that the patient does not have ITP. R.M. and D.K. designed the study. R.M., M.S., and D.K. analyzed the data and interpreted the results. O.Z. conducted the experimental work. All authors contributed to the writing of the manuscript. The authors acknowledge the assistance of Hang Lee from Harvard Catalyst for statistical support. ""Disease Overview: Chronic lymphocytic leukemia (CLL) is the commonest leukemia in western countries. The disease typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that impair apoptosis of clonal B-cells.