Mechanisms of abnormal erythropoiesis in malignancy

In order the investigate mechanisms of diminished red cell production in malignancy, we assayed erythroid progenitor cell proliferative responses to erythropoietin in plasma clot cultures of bone marrow cells from 34 cancer patients. Erythroid colony growth by marrow cells of 11 healthy donors (means of 58 CFU-E and 19 BFU-E derived colonies/6 X 10(4) cells) was similar to that in cultures of cells from patients either with (means of 44 CFU-E and 22 BFU-E derived colonies/6 X 10(4) cells) or without (means of 50 CFU-E and 19 BFU-E derived colonies/6 X 10(4) cells) myelophthisis. Colony formation was normal at all erythropoietin concentrations tested, indicating that both the CFU-E and BFU-E retain normal erythropoietin sensitivity in vitro. CFU-E proliferation correlated negatively (r = -0.56; P less than 0.001) with the level of hemoglobin. In contrast to marrow cell proliferative responses to erythropoietin, serum erythropoietin levels were inappropriately reduced in all 19 patients in whom they were measured, a finding which may be important in the pathogenesis of anemia in patients with cancer.