Effects of hexadecylphosphocholine on thrombocytopoiesis

HexadecylphosphochoIine (HePC) is the first representative of the alkylphos phocholines, a novel group derived from the cytotoxic etherlysophospholipid s. HePC shows a broad spectrum of antiproliferative effects in neoplastic c ells in vitro and in vivo. HePC has been tested successfully in several cli nical studies. One of the remarkable features of this compound has been the induction of a leucocytosis and a thrombocytosis in most of the patients r eceiving HePC systemically. In this paper, we have investigated the biologi cal and molecular mechanisms by which HePC exerts this interesting effect. We found that HePC acts as an unspecific costimulator on human megakaryocyt ic proliferation in a soft agar assay system predominately together with th rombopoietin (TPO). Furthermore, HePC leads to the synthesis and secretion of several haematopoietic growth factors in monocytes and bone marrow fibro blasts, determined by the direct measurement of growth factors in cellular supernatants and by the measurement of growth factor mRNA in cell extracts. Thus, HePC seems to produce the increase of blood platelets in tumour pati ents by two different mechanisms. (C) 2001 Elsevier Science Ltd. All rights reserved.