ABSTRACT
Chronic myeloproliferative disorders (MPD) include a spectrum of diseases characterized by excess clonal proliferation of one or more myeloid lineages in the bone marrow with cell maturation being relatively normal. Excess proliferation results in increased numbers of leukocytes, red cells, and/or platelets in the peripheral blood, and is frequently associated with splenomegaly and hepatomegaly. The original classification proposed by Dameshek included four related chronic MPD, often referred to as ‘classical ’ MPD and currently called chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). 1 Although many people considered that CML was distinct from the other three disorders, Dameshek ’ s suggestion that his classification ‘may prove useful and even productive ’ was dramatically borne out by the finding that chronic MPD, at least as far as we know at present, have a common root cause: aberrant activation of tyrosine kinase signaling as a result of specific acquired mutations that results in clonal, stem cell-derived hyperproliferation. The importance of tyrosine kinases was of course highlighted by the finding and characterization of BCR-ABL in CML, 2-4 but a clear pointer towards the wider involvement of this class of signaling proteins in the pathogenesis of MPD came from the study of so-called ‘atypical ’ MPD, a heterogeneous group of diseases that are the subject of this review.
