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Introduction

The concept of the myeloproliferative disorders (MPD) or myeloproliferative neoplasms (MPN) as a group of closely related disorders was formulated by William Dameshek in 1951 [1]. His editorial on this subject commenced with the words "With accumulating experience, it becomes more and more evident that the bone marrow cells - erythroblasts, granulocytes, megakaryocytes - often proliferate en masse or as a unit rather than as individual elements." The six disorders he included in this group were chronic granulocytic leukaemia, polycythaemia vera, thrombocythaemia, megakaryocytic leukaemia, idiopathic or agnogenic myeloid metaplasia of the spleen (and liver) and erythroleukaemia (di Guglielmo's syndrome). The concept of a group of related disorders was based on shared features and on the observation of transitional forms and the evolution of one condition into another. There was at this stage no conception of the neoplastic nature of these conditions. Dameshek suspected that the cause was a myelostimulatory factor, perhaps adrenocorticotropic hormone. He also viewed the myelofibrosis as an intrinsic part of the disease with reticulum cells and fibroblasts participating in the process.

With the advances in knowledge in the last 50 years it is now possible to refine Dameshek's ideas. The MPN are now known to be haematological neoplasms characterized, at least in their early stages, by effective proliferation of myeloid cells of at least one lineage. The World Health Organization (WHO) classification now suggests use of the term 'myeloproliferative neoplasm'. Evolution to myelofibrosis is possible in all. The myeloid metaplasia in the spleen and liver is, as Dameshek suspected, an intrinsic part of these disorders, not a compensatory phenomenon, but the fibrosis is a reactive process. All of these conditions have the potential to evolve into acute myeloid leukaemia (AML) but with a variable frequency. Transformation is common in chronic granulocytic leukaemia (see below) and less common in other MPN.

With the discovery 35 years ago of a recurrent cytogenetic abnormality, t(9;22)(q34;q11) [2, 3] and the subsequent discovery of the BCR-ABL1 fusion gene [4] in chronic granulocytic leukaemia, it was recognized as a quite distinct entity within the MPN. Recent scientific advances have confirmed the close relationship of polycythaemia vera, essential thrombocythaemia and idiopathic myelofibrosis. In 2005 four groups almost simultaneously described a point mutation in the JAK2 gene, JAK2 V617F, which is present in virtually all cases of polycythaemia vera and in about half of cases of essential thrombocythaemia and idiopathic myelofibrosis [5-9]. A point mutation in the MPL gene, MPL W515L, is found in a lower percentage of cases of essential thrombocythaemia and idiopathic myelofibrosis (Figure 3.1). Cases of essential thrombocythaemia with a JAK2 mutation have disease features closer to polycythaemia vera than do other cases.

Figure 3.1

Diagram showing the frequency of JAK2 V617F (blue) and MPL W515L (red) mutations in patients with polycythaemia vera, essential thrombocythaemia and chronic idiopathic myelofibrosis.

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