The Platelet-cancer Loop in Myeloproliferative Cancer. Is Thrombocythemia an Enhancer of Cancer Invasiveness and Metastasis in Essential Thrombocythemia, Polycythemia Vera and Myelofibrosis?

Recent studies have provided evidence that the Philadelphia-negative chronic myeloproliferative neoplasms, essential thrombocythemia, polycythemia vera and myelofibrosis (MPNs), may be preceded or accompanied by chronic inflammation and are associated with an increased risk of second cancers, both hematological and non-hematological. Thrombocythemia is one of the hallmarks in the early stages of these neoplasms. Several non-hematological cancers are associated with reactive thrombocythemia, which has been shown to have a major negative impact upon survival. In regard to treatment of MPNs a "wait and watch" strategy is recommended in patients with low-risk disease. Another strategy implies early treatment with interferon-alpha2 (IFN) to prohibit clonal evolution. Based upon experimental and clinical studies of the important role of platelets for cancer invasiveness and metastasis it is herein argued, that these detrimental platelet effects further support the "Early Interferon Concept" in MPNs to normalize elevated leukocyte and platelet counts. In the context of the known increased risk of second cancer in MPNs the prevailing "wait and watch" strategy is seriously challenged, when taking into account that this strategy may actually worsen prognosis of second cancers in MPNs due to elevated platelet counts, enhancing cancer invasiveness and its metastatic potential.