Myeloproliferative neoplasms
(MPN)
Myeloproliferative neoplasias (MPN) are brood diseases that are caused by an excessive production of blood cells in the bone marrow. MPN arise from one or more acquired genetic changes (mutations) in a blood stem cell, which lead to the multiplication of this mutated stem cell and the clinical picture of MPN.
The diagnosis of MPN according to the classification of the World Health Organization (WHO) includes increased cell counts in the peripheral blood, changes in the bone marrow and the aforementioned acquired mutations in the blood cells.
The MPN in the narrower sense (also called BCR-ABL1 negative MPN) include polycythemia vera (PV), essential thrombocytemia (ET) and primary myelofibrosis (PMF). In PV, especially the red blood cells and in ET the blood platelets are increased, in PMF the increased blood formation leads to fiber formation in the bone marrow with a shift of blood formation to the spleen.
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Pathogenesis
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In around 90% of patients with MPN, a mutation can be found in one of the three previously known so-called "driver genes", Janus kinase 2 (JAK2), calreticulin (CALR), or thrombopoietin receptor (MPL), which trigger MPN can. In around half of MPN patients, there are also mutations in other genes that can influence the course of the disease. The meaning of the individual mutations and the resulting consequences are currently being intensively researched.
Symptoms and Findings
In addition to changes in the blood count, fatigue, reduced performance and night sweats are possible symptoms of MPN. With ET and PV, circulatory disorders of the small blood vessels (tingling in the hands and feet) occasionally occur, and with PV, itching occurs. In advanced stages of MPN an enlargement of the spleen can be detected, which can lead to a feeling of pressure in the left upper abdomen. The serious complications of MPN include thrombosis and/ or bleeding, and progression to myelofibrosis with bone marrow failure, or transition to acute leukemia.
Therapeutic options
The use of tyrosine kinase inhibitors (TKIs) has improved the treatment of many tumor diseases. In the case of MPN, Janus kinase inhibitors are available today, which are used in PMF with disease-related symptoms and/or enlarged spleen, but also increasingly in PV. Hydroxyurea and interferon are other therapies that can be used in MPN patients at increased risk of thrombosis. Blood stem cell transplantation can also be considered in PMF patients, which is the only curative treatment option. In the different areas of diagnostics and therapy, there are currently many new therapy options and, based on more detailed diagnostic criteria, a more comprehensive picture of the MPN.
With the MPN Register and the support of MPN Research, the Foundation MPN Research Switzerland would like to contribute to further improving the treatment options for MPN.
Diagnosis
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New treatment options and different survival rates require a reliable differentiation of the neoplasms belonging to the group of MPN. Especially in the early stages, which often present as persistent thrombocytosis, the differential
diagnosis is complicated. Only a synopsis of hematological, molecular genetic, cytological and histomorphological findings enables the correct classification of the disease - this is extremely important for adequate therapy.
Source: Arber et al .: The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia In: Blood. Volume: 127, Issue: 20, 2016
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