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Changes in Glycosphingolipid Composition during Differentiation of Human Leukemic Granulocytes in Chronic Myelogenous Leukemia Compared with in Vitro Granulocytic Differentiation of Human Promyelocytic Leukemia Cell Line HL-60¹

Division of Hemopoiesis, Institute of Hematology [H. N., M. O., M. S.], and Division of Hematology [Y. M.], Jichi Medical School, Minami-kawachi-machi, Kawachi-gun, Tochigi-ken 329-04, and The Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Hongo, Tokyo 113 [F. T.], Japan

Changes in glycosphingolipid (GSL) composition during differentiation of human leukemic granulocytes were investigated qualitatively and quantitatively in immature and mature granulocytic cells derived from human chronic myelogenous leukemia (CML) cases and were compared with those found in the in vitro granulocytic differentiation of the human promyelocytic leukemia HL-60 cell line. Two neutral GSLs, ceramide monohexoside and ceramide dihexoside, and two molecular species of gangliosides, one being the ganglio-series ganglioside NeuAc(2-3)Gal(ß1-4)Glc-Cer (G_M3) and the other being the lacto-series sialosylparagloboside, were predominant in the granulocytic cells at an early maturation stage. During the granulocytic differentiation of CML cells, the contents of ceramide dihexoside and paragloboside increased strikingly with a concomitant decrease in ceramide monohexoside, and the total amount of neutral GSLs increased to about three times as much as that of the most immature granulocytic cells, myeloblasts. On the other hand, lacto-series gangliosides, with longer sugar moieties increased with a concomitant decrease in ganglio-series ganglioside G_M3, and the ganglioside profile became more complex. The total content of ganglioside increased in parallel with the complexity of the ganglioside profile. Similar differentiation-associated changes were also found in GSL composition during the in vitro granulocytic differentiation of HL-60 cells. However, a marked difference between the differentiation-dependent change in the GSL composition of CML cells and that of HL-60 cells was observed for a ganglioside species which was found to be one of the major gangliosides in normal neutrophils: in the former, the ganglioside level increased up to the level in normal mature granulocytes as the cells differentiated; in contrast, it decreased significantly during granulocytic differentiation of the latter cells.

When the GSL composition of the neutrophils obtained from CML cells, which were apparently normal as to morphology, stimulus-induced membrane potential changes, and superoxide-producing capacity, was compared with that of normal neutrophils, an obvious difference was observed between them, especially with regard to ganglioside G_M3; the amount of ganglioside G_M3 in the former was about one-sixth of that in the latter. This finding indicates some alterations in the cell membrane structure of neutrophils of CML origin.

¹ Supported in part by Grants-in-Aid from the Ministry of Education, Science and Culture, Japan.

² To whom requests for reprints should be addressed.

Received 6/12/85. Accepted 8/26/85.