Abnormal modulation of granulocyte/macrophage progenitor proliferation by prostaglandin E in chronic myeloproliferative disorders.
The effect of prostaglandin E1 (PGE1) on the in vitro proliferation of peripheral blood granulocyte/macrophage progenitors (CFUc) from the patients with chronic myeloproliferative disorders was examined. PGE1 was found to be a dose-dependent inhibitor of normal peripheral blood and bone marrow CFUc. Peripheral blood CFUc from patients with chronic myelogenous leukemia (CML) showed normal inhibition when cultured in the absence of exogenous colony stimulating factor (CSF). The addition of CSF to CML peripheral blood cultures resulted in complete abrogation of normal PGE1 inhibition. Dose-titration studies in which increasing amounts of CSF were added to CML cultures showed decreasing PGE1 inhibition with increasing CSF concentration. This observation indicated increased efficiency of competition between the colony stimulating effect of CSF and the colony inhibitory effect of PGE1 in CML. Peripheral blood CFUc from patients with myelofibrosis/myeloid metaplasia (MM) showed heterogeneous responses to PGE1 with complex dose-effect curves showing variable combinations of stimulation and inhibition of CFUc proliferation. Further studies showed that these effects of PGE1 were blocked by the prostaglandin antagonist SC-19220, and were not due to elaboration of CSF or non-CSF enhancers of CFUc proliferation from MM adherent cells. Cell fractionation studies in 2 patients, with MM showed dual populations of CFUc, one responding abnormally, and another normally to PGE1, accounting in part for the complex dose-response curves. These studies indicate that significant abnormalities exist in the in vitro response to PGE1 by CFUc from patients with chronic myeloproliferative disorders. Deficiencies in PGE 1 inhibition may contribute to the excess myelopoiesis seen in these disorders.
D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000276:immunology; D006098:Granulocytes / Q000276:immunology; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D009196:Myeloproliferative Disorders / Q000276:immunology*; D055728:Primary Myelofibrosis / Q000276:immunology; D011458:Prostaglandins E / Q000494:pharmacology*
D003115:Colony-Stimulating Factors; D011458:Prostaglandins E