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Ether-linked Phosphoglyceride Content of Human Leukemia Cells¹

Departments of Medicine [M. C. C., R. L. C.], Biochemistry [M. C. C., D. G. G., R. L. W.], and Prevention Research [J. K. B.], and the Cancer Center of Wake Forest University, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27103

The glycerolipids of most cells are characterized by a specific proportion of ether linkages at the sn-1 position of the glycerol backbone. A number of tumors are known to have altered concentrations of ether-linked lipids compared to normal tissues. However, no through examination of the ether-lipid content of human leukemia cells has been reported despite the importance of these lipids in normal leukocyte function. In the present study samples were obtained from adults with acute myelogenous leukemia (AML), chronic granulocytic leukemia in blast crisis, and acute lymphocytic leukemia and from healthy human donors. The cellular lipids were extracted, the individual phospholipid classes were isolated, lipid phosphorus content was determined, and the lipids were converted to diglyceride benzoate derivatives for separation and quantitation of the subclasses by high performance liquid chromatography. The data indicate that all the leukemic cells analyzed have an altered phospholipid composition compared to their respective normal leukocytes. Furthermore, among the AML patients both the percentage of the choline-containing phosphoglyceride fraction (PC) which is alkyl linked and the nmoles alkyl-PC/10⁶ cells differ significantly by FAB subtype. A positive correlation between the levels of alkyl-PC and the degree of cellular differentiation is observed. Although no differences are observed between chronic granulocytic leukemia in blast crisis and AML lipids, the leukemic cells contain dramatically lower levels of alkyl-linked PC than do normal polymorphonuclear leukocytes. In contrast, no differences are observed between the alkyl-PC content of normal and leukemic lymphocytes. In light of the relations among ether-lipids, protein kinase C, and cell differentiation, these data suggest the ether-linked lipids are important in myeloid cell function and differentiation.

¹ This work was supported in part by the Leukemia Cell Procurement and Biostatistics shared facilities of the Cancer Center of Wake Forest University (CA 12197) and by NIH Grant HL-26818.

² To whom requests for reprints should be addressed, at Department of Biochemistry, Bowman Gray School of Medicine of Wake Forest University, 300 So. Hawthorne Road, Winston-Salem, NC 27103.

Received 4/23/90. Accepted 8/14/90.

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