Progression of myeloproliferative neoplasms to myelofibrosis and acute leukaemia

Bcr-abl-negative myeloproliferative neoplasms (MPN), comprising polycythaemia vera (PV), primary myelofibrosis (PMF) and essential thrombocythaemia (ET), usually follow a biphasic course. From a phase which is characterized by excess production of mature haematopoietic cells of one or more lineages, many, but not all MPN, progress to haematopoietic insufficiency with cytopenia affecting two or three lineages. The latter may be the result of either fibrosis, blastic transformation or both. An intermediate stage of variable duration is called acceleration. Unlike bcr-abl-positive chronic myeloid leukaemia (CML), acceleration in MPN is not homogeneously defined. Long-lasting PV may progress to a PMF-like myelofibrosis, labelled spent phase. Less frequently, PV develops into a myelodysplastic/myeloproliferative neoplasm (MDS/MPN) resembling either atypical CML or chronic myelomonocytic leukaemia. Progression in PMF and ET leads either to advanced osteomyelofibrosis or to MDS/MPN with fibrosis. CML and bcr-abl-negative MPN share the same definition for transformation with ≥20% blasts in the blood or bone marrow. Transformation to blast crisis can occur at any stage in MPN and is more likely in PMF and PV than ET. There are different molecular pathways to progression. In a subset of MPN, transformation is accompanied by the occurrence of a complex karyotype.