Myeloproliferative Neoplasms (MPN) – Overview
Dipl.-Ing. (FH) Tanja Hinrichsen
MPN comprise a group of clonal hematopoietic stem cell disorders, which are characterized by proliferation of one or several members of the myeloid cell line. MPN predominantly occure in adults, age between 50 and 70 (incidence approx. 6–10:100,000/year), and is divided into 2 categories:
- Ph-positive chronic myeloid leukemia (see also CML)
- Ph-negative myeloproliferative neoplasms (PV, ET, PMF, see also respective chapters)
Chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia (CEL) (also hypereosinophilic syndrome (HES)) and mastocytosis belong to the less frequently occurring disorders. Myelodysplastic/myeloproliferative neoplasms which include the chronic myelomonocytic leukemia (CMML), the BCR-ABL negative atypical CML and the juvenile myelomonocytic leukemia (JMML) represent another group. Since CML, polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) overlap in their biological and clinical features, CML should be ruled out first, which can be done by cytogenetic detection of a philadelphia translocation t(9;22)(q34;q11.2) using chromosome analysis, FISH or moleculargenetic analysis. Most MPN are associated with acquired genetic abnormalities affecting cytoplasmic or receptor tyrosine-kinases. Translocations or point mutations in these genes lead to constitutively activated tyrosine-kinases and an abnormal increase in cell proliferation. Mutations in the JAK2 gene play a major role in the pathogenesis of PV, ET and PMF. In systemic mastocytosis, however, the D816V mutation in the KIT gene is usually present, which encodes a receptor tyrosine-kinase. In MPN with eosinophilia, rearrangements of the genes PDGFRA (4q12), PDGFRB (5q31-q33) and FGFR1 (8p11) should be detected or ruled out using chromosome analysis or FISH.