Complex carbohydrates as differentiation markers in malignant blood cells: glycolipids in the human leukemias

This article summarizes the data on chemical sequencing of human leukocyte cell surface glycolipids that we have obtained over the last 3 years. The purpose of the work was to determine if these cell surface glycoconjugates differ among different leukocyte populations and at different stages of development. In homogeneous form we purified large numbers of leukocytes from normal persons and persons with acute and chronic leukemias of myeloid and lymphoid types, using continuous flow centrifugation leukapheresis. We extracted the glycolipids from these cells and used thin-layer chromatography, gas-liquid chromatography, gas chromatography-mass spectrometry, direct probe mass spectrometry, and enzyme treatment to obtain complete structural information on these compounds. Twenty glycolipids were identified and sequenced, representing over 99% of the glycolipids of human leukocytes. The major findings are that human leukocytes possess glycolipid patterns that distinguish them from other blood cells. Additionally, leukocytes of "myeloid' and "lymphoid' types can be distinguished by their glycolipid type. Glycolipids in human leukemic cells show two main features: (1) even though the cells appear morphologically "undifferentiated', all leukemias can be classified on the basis of their glycolipids as "myeloid' or "lymphoid'; (2) the complexity of their cell surface glycolipids is correlated with their degree of morphologic "differentiation', the more differentiated leukemias having more complex structures. No glycolipids were found in leukemic leukocytes that were not found in the normal cells. Glycolipids would therefore appear to be useful as both cell- and possibly differentiation-specific markers in human blood cells. The antigenic differences seen in human leukemic cells may be due in part to an altered distribution of complex carbohydrates at the cell surface.