Polycythemia vera: myths, mechanisms, and management.

Polycythemia vera is a clonal disorder arising in a multipotent hematopoietic progenitor cell that causes the accumulation of morphologically normal red cells, white cells, platelets, and their progenitors in the absence of a definable stimulus and to the exclusion of nonclonal hematopoiesis.1,2 First described in 1892,3 polycythemia vera is not a new disease and while uncommon, with an incidence of at least 2 per 100 000,4-6 it is not a rare disease. Yet, after 10 decades of careful clinical and laboratory investigation, the etiology of polycythemia vera remains unknown and there is no consensus as to the optimal therapy for the disorder.7 There is, however, no reason for this to be so. Although the molecular basis of polycythemia vera remains elusive, it is the central thesis of this review that the pathophysiology of polycythemia vera is sufficiently well defined for the provision of a rational treatment program that prolongs life, alleviates the specific morbidities associated with the disease, and avoids complications related to the consequences of the underlying molecular defect. However, for such an approach to be successful, it is first necessary to recognize the contradictions between what is actually known about this disease and how that knowledge has been interpreted and applied clinically, and that is the purpose of this review.