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

Changes in glycosphingolipid (GSL) composition during differ entiation 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(a2-3)Gal(j31 4)Glc-Cer (GM3)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 con comitant decrease in ganglio-series ganglioside GM3, and the ganglioside profile became more complex. The total content of ganglioside increased in parallel with the complexity of the gan glioside 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 com position 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 superoxideproducing capacity, was compared with that of normal neutro phils, an obvious difference was observed between them, es pecially with regard to ganglioside GMS;the amount of ganglioside GM3in the former was about one-sixth of that in the latter. This Received 6/12/85; accepted 8/26/85. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1Supported in part by Grants-in-Aid from the Ministry of Education, Science and Culture, Japan. 2To whom requests for reprints should be addressed. finding indicates some alterations in the cell membrane structure of neutrophils of CML origin.