Cytokines, endothelium, and adhesive molecules in pathologic thrombopoiesis

Clonal thrombocytosis (CT) associated with my eloproliferative disorders (M PD) is believed to be secondary to autonomous unregulated platelet producti on. Secondary or reactive thrombocytosis (RT) can be observed in a number o f clinical circumstances and may be related to persistent production of som e thrombopoietic factors acting on megakaryocytes (MK). The goal of this st udy is to assess the serum concentrations of these cytokines in control sub jects and patients with MPD associated with thrombocythemia, RT, and autoim mune thrombocytopenic purpura (ATP). Eleven patients with MPD, five with ch ronic myeloid leukemia (CML), three with polycythemia vera (PCV), two with essential thrombocythemia (ET), one with myelofibrosis, 15 with RT, eight w ith ATP, and 12 healthy volunteers were enrolled in the study. Serum interl eukin (IL)-1 beta, IL-6, tumor necrosis factor-alpha (TNF), fibronectin, in tracellular adhesion molecule-1 (ICAM-1), and thrombomodulin (TM) were meas ured in these groups. Interleukin-1 beta, IL-6, and TNF levels were high in patients with RT and ATP, suggesting that these cytokines act on early uncommitted progenitors, promoting commitment along the MK lineage and leading to thrombocytosis or compensation for thrombocytopenia. TM was significantly increased in patien ts with MPD compared to all other groups, probably indicating the presence of subclinical endothelial damage. Fibronectin levels were high in MPD and RT patients. This finding can be secondary to high platelet turnover in the se patients. We found that ICAM-1 levels were high in patients with clonal thrombocytosis. ICAM-1 can be one of the factors initiating the events ulti mately leading to clonal thrombocytosis. Thrombocythemia associated with MP D is an autonomous phenomenon not regulated by cytokines.