Chronic Myeloproliferative Neoplasms: Clinical and Molecular Genetics

Chronic myeloproliferative neoplasms (previously called myeloproliferative diseases) are group of haematopoietic neoplasms characterised by clonal proliferation of differentiated cells from the myeloid lineage. This includes granulocytes, erythrocytes and megakaryocytes. In general, the course of these neoplasms is chronic and some patients may live more than 20 years and die from other causes, however, in some patients, they may manifest aggressively and kill patients in short time. Significant progress have been made in understanding the molecular basis of these diseases and recently new pharmaceutical agents have been developed that specifically target these molecular abnormalities and converted these neoplasms to chronic diseases to live with as any other chronic disease. We find in this group of diseases chronic myeloid leukaemia and polycythaemia vera, which are perhaps the most molecularly defined two neoplasms. The BCR-ABL1 fused gene is the cause of the first neoplasm and the mutated JAK2 gene cause the second disease, both of which are targeted in the current treatment of these two diseases. Key Concepts Mutations cause the uncontrolled growth of cells, but these cells are capable of differentiation. The ability of these leukaemic cells to differentiate leads to their death at some point making these diseases less aggressive than acute leukaemias. Chromosomal translocations and mutations in specific genes are implicated in these groups of diseases. Most of the genomic abnormalities in these diseases lead to activating specific kinases and this leads to uncontrolled cell proliferation. By targeting these kinases, cell growth can be controlled and these diseases can be managed successfully. Translocations may lead to fusing two genes and the expression of a fused protein or may lead to a change in the regulation of the gene and its deregulation. Activation of a gene via translocation is usually into other genomic locus and a specific partner gene, but occasionally can be promiscuous and accept other partners. Historically the Philadelphia chromosome is considered the first hint for the fact cancer is genomic disease was discovered in CML, which is one of the cMPNs discussed here. Keywords: chronic myeloid leukaemia; eosinophilia; mastocytosis; myeloproliferative neoplasms; Philadelphia chromosome; BCR-ABL; polycythaemia vera; myelofibrosis; essential thrombocythaemia