Leukemia Research 38 (2014) 1230–1236
Contents lists available at ScienceDirect
Leukemia Research journal homepage: www.elsevier.com/locate/leukres
The platelet–cancer loop in myeloproliferative cancer. Is thrombocythemia an enhancer of cancer invasiveness and metastasis in essential thrombocythemia, polycythemia vera and myelofibrosis? Hans Carl Hasselbalch ∗ Department of Hematology, Roskilde Hospital, University of Copenhagen, Køgevej 7-13, 4000 Roskilde, Denmark
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Article history: Received 5 May 2014 Received in revised form 26 June 2014 Accepted 14 July 2014 Available online 22 July 2014 Keywords: Myeloproliferative cancer Thrombocythemia Second cancer Cancer invasiveness Metastasis Interferon Statins
a b s t r a c t 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. © 2014 Elsevier Ltd. All rights reserved.
1. Introduction The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) – essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) – are closely related acquired stem cell neoplasms characterized by transitions between the diseases, implying a biological continuum from ET over PV to the advanced myelofibrosis phase—either categorized as PMF or myelofibrosis following ET and PV [1]. Recent studies have provided evidence that MPNs may be preceded by or accompanied by chronic inflammation [2–5] and may also imply an increased risk for the development of other cancers, both hematological and non-hematological [6–9]. Furthermore, it has been argued that chronic inflammation and accumulation of reactive oxygen species (ROS) may have a major role for clonal evolution and development of second cancers in MPNs [3–5]. In regard to treatment of MPNs a “wait and watch” strategy is recommended in patients with low-risk disease, allowing leukocytosis and elevated platelet counts up to 1500 Mia/L in patients
Contents lists available at ScienceDirect
Leukemia Research journal homepage: www.elsevier.com/locate/leukres
The platelet–cancer loop in myeloproliferative cancer. Is thrombocythemia an enhancer of cancer invasiveness and metastasis in essential thrombocythemia, polycythemia vera and myelofibrosis? Hans Carl Hasselbalch ∗ Department of Hematology, Roskilde Hospital, University of Copenhagen, Køgevej 7-13, 4000 Roskilde, Denmark
a r t i c l e
i n f o
Article history: Received 5 May 2014 Received in revised form 26 June 2014 Accepted 14 July 2014 Available online 22 July 2014 Keywords: Myeloproliferative cancer Thrombocythemia Second cancer Cancer invasiveness Metastasis Interferon Statins
a b s t r a c t 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. © 2014 Elsevier Ltd. All rights reserved.
1. Introduction The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) – essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) – are closely related acquired stem cell neoplasms characterized by transitions between the diseases, implying a biological continuum from ET over PV to the advanced myelofibrosis phase—either categorized as PMF or myelofibrosis following ET and PV [1]. Recent studies have provided evidence that MPNs may be preceded by or accompanied by chronic inflammation [2–5] and may also imply an increased risk for the development of other cancers, both hematological and non-hematological [6–9]. Furthermore, it has been argued that chronic inflammation and accumulation of reactive oxygen species (ROS) may have a major role for clonal evolution and development of second cancers in MPNs [3–5]. In regard to treatment of MPNs a “wait and watch” strategy is recommended in patients with low-risk disease, allowing leukocytosis and elevated platelet counts up to 1500 Mia/L in patients
