title: Angiogenesis in myeloproliferative neoplasms, new markers and future directions.
abstract: Tumor angiogenesis has been identified to play a critical role in tumor growth and tumor progression, and is regulated by a balance of angiogenic and antiangiogenic cytokines. This has been documented for solid tumors, and there is emerging evidence suggesting that tumor progression of hematological malignancies also depends on the induction of new blood vessel formation. Data on angiogenesis in the bone marrow of BCR-ABL1-negative myeloproliferative neoplasm patients suggest an increase of the microvessel density and vascular endothelial growth factor (VEGF) expression, and there is a relation to the JAK2-V617F status. The most important proangiogenic agent is VEGF, activating VEGF receptors 1 and 2. Inhibition of VEGF signaling by monoclonal antibodies or small molecules (kinase inhibitors) has already been successfully established for the treatment of different cancer entities, and multiple new drugs are being tested in clinical trials. Most patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF) that was not associated with a JAK2 or MPL alteration carried a somatic mutation in calreticulin (CALR). Thus, CALR mutations should be included in the next classification system for ET/PMF. This review summarizes recent advances in the basic understanding of the role of angiogenesis in myeloproliferative neoplasms and the translation of such basic findings into clinical studies.
authors.affiliation: Department of Hematology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Medinger
authors.affiliation: Department of Hematology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
authors.forename: Jakob
authors.initials: J
authors.lastname: Passweg
keywords: Angiogenesis; Microvessel density; Myeloproliferative neoplasms; Primary myelofibrosis; Vascular endothelial growth factor