Myeloproliferative Neoplasms

The myeloproliferative neoplasms - polycythemia vera, essential thrombocytosis, and primary myelofibrosis - are unique hematopoietic stem-cell disorders that share mutations that constitutively activate the physiologic signal-transduction pathways responsible for hematopoiesis (Table 1). Consequently, these disorders engage in phenotypic mimicry among themselves, as well as with myeloid neoplasms and even benign hematopoietic disorders. In contrast to the myeloid neoplasms, the myeloproliferative neoplasms have a natural history, with supportive care alone, that is usually measured in decades rather than years. 1 However, a facade of benign myeloproliferation masks a clone of transformed hematopoietic stem cells capable of expansion and transformation to an aggressive form of bone marrow failure or acute leukemia, albeit at varying frequencies in each of these disorders. In addition to phenotypic mimicry, each type of myeloproliferative neoplasm is capable of evolving into another type, making diagnosis, risk assessment, and therapeutic choices difficult. Furthermore, despite more than a century of scrutiny, the pathogenesis of myeloproliferative neoplasms has been enigmatic, and therapy largely supportive. Recently, however, driver mutations have been identified in more than 90% of patients with myeloproliferative neoplasms, providing substantial insight into their pathogenesis. The current challenge is to integrate this new knowledge with the accumulated decades of clinical knowledge to improve diagnosis, risk assessment, and therapy.