BONE-MARROW PURGING IN ACUTE-LEUKEMIA WITH ALKYL-LYSOPHOSPHOLIPIDS - A NEW FAMILY OF ANTICANCER DRUGS

被引：18

作者：

VOGLER, WR

机构：

[1] Emory University, Department of Medicine, Division of Hematology and Oncology, Atlanta

来源：

LEUKEMIA & LYMPHOMA | 1994年 / 13卷 / 1-2期

关键词：

EDELFOSINE; AUTOLOGOUS BONE MARROW TRANSPLANTATION; LEUKEMIA;

D O I：

10.3109/10428199409051652

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The alkyl-lysophospholipids are a new family of anticancer drugs which target the cell membrane as their site of action. Enzymes involved in signal transduction (protein kinase C and phosphatidylinositol phospholipase C), phospholipid biosynthesis (lysophosphatidyl acyltransferase and CTP:cholinephosphate cytidylyltransferase) and maintenance of membrane integrity (Na,K ATPase sodium pump) are inhibited. A unique feature of the alkyl-lysophospholipids is their selective cytotoxicity to neoplastic cells. This suggests that the compound would be an excellent agent for purging residual leukemic cells from marrows of patients in remission prior to autologous bone marrow transplantation. Preclinical studies in a murine leukemia model and in an in vitro human system demonstrated successful elimination of leukemic cells from a mixture of normal and leukemic marrows. Twenty-nine poor risk patients with acute leukemia underwent autologous bone marrow transplantation and were reinfused with marrow treated in vitro with edelfosine. Nine of these patients remain in remission free of leukemia from 368 to 1369 days. These encouraging results warrant further investigation.

引用

页码：53 / 60

页数：8

共 53 条

[1]

Lee T.-C., Snyder F., Function, metabolism, and regulation of platelet activating factor and related ether lipids, Phospholipids and Cellular Regulation, 2, pp. 2-39, (1985)

[2]

Pirotzky E., Hosford D., Mencia-Huerta J.-M., Bra-Quet P., Role of platelet-activating factor in immune process, Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation and Radiation Injury, pp. 427-437, (1991)

[3]

Andreesen R., Modolell M., Weltzien H.U., Eibl H., Common H.H., Lohr G.W., Munder P.G., Selective destruction of human leukemic cells by alkyl-lyso-phospholipids, Cancer Res., 38, pp. 3894-3899, (1978)

[4]

Modolell M., Andreesen R., Pahlke W., Brugger U., Munder P.G., Disturbance of phospholipid metabolism during the selective destruction of tumor cells induced by alkyl-lysophospholipids, Cancer Res., 39, pp. 4681-4686, (1979)

[5]

Vogler W.R., Whigham E.A., Somberg L.B., Long R.C., Winton E.F., The effect of alkyl-lyso phospholipids on tritiated thymidine incorporation and clon-ogenicity in vitro of normal and leukemic human cells, Exp. Hematol., 12, pp. 569-574, (1984)

[6]

Hoffman D.R., Hajdu J., Snyder F., Cytotox-icity of platelet activating factor and related alkyl-phospho-lipid analogs in human leukemia cells, polymorphonuclear neutrophils, and skin fibroblasts, Blood, 63, pp. 545-552, (1984)

[7]

Schick H.D., Berdel W.E., Fromm M., Fink U., Jehn U., Ulm K., Reichert A., Eibl H., Unger C., Rastetter J., Cytotoxic effects of ether lipids and derivatives in human non-neoplastic bone marrow cells and leukemic cells in vitro, Lipids, 22, pp. 904-910, (1987)

[8]

Verdonck L.F., Witteveen E.O., van Heugten H.G., Rozemuller E., Rijksen G., Selective killing of malignant cells from leukemic patients by alkyl-lysophospho-lipid, Cancer Res., 50, pp. 4020-4025, (1990)

[9]

Helfman D.M., Barnes K.C., Kinkade J.M., Vogler W.R., Shoji M., Kuo J.F., Phospholipid-sen-sitive Ca2+-dependent protein phosphorylation system in various types of leukemic cells from human patients and in hu man leukemic cell lines HL60 and K562, and its inhibition by alkyl-lysophospholipid, Cancer Res., 43, pp. 2955-2961, (1983)

[10]

van Blitterswijk W.J., van der Bend R.L., Kramer I.M., Verhoeven A.J., Hilkmann H., de Widt J., A metabolite of an antineoplastic ether phospholipid may inhibit transmembrane signalling via protein kinase C, Lipids, 22, pp. 842-846, (1987)

← 1 2 3 4 5 6 →