Classification and Molecular Biology of Polycythemias (Erythrocytoses)

Abstract

The name “polycythemia” is derived from the Greek and means literally “too many cells in the blood”. Thus, only an increase in red cells constitutes polycythemia. In the clinical setting polycythemia exists when the hemoglobin and red blood cell count are increased, reflecting an elevation of the total red blood cell volume. Polycythemias can be differentiated based on the responsiveness of the erythroid progenitors to circulating cytokines. Primary polycythemias are characterized by an excessive response of the erythroid progenitors to circulating cytokines, as a result of acquired somatic or inherited germline mutations that are expressed within hematopoietic progenitors causing increased proliferation and or decreased apoptosis, resulting in the accumulation of red cells. In terms of oxygen demand and oxygen requirements, primary polycythemias can be viewed as the production of the oxygen carrying capacity (hemoglobin) fully dissociated from the tissue oxygen needs and from the oxygen sensing pathway. In contrast, secondary polycythemias are characterized by a normal responsiveness of the erythroid progenitors to circulating cytokines and an increased level of circulating factors driving erythropoiesis, e.g., erythropoietin (EPO), insulin-like growth factor-I (IGF-I), cobalt, etc. Thus, in terms of oxygen demand, secondary polycythemias can be viewed as a physiological response to satisfy the oxygen needs of the tissues, or the germline or somatic mutations disturbing the oxygen sensing pathway or its target, i.e., EPO.