Regulation of O-acetylation of sialic acids by sialate-O-acetyltransferase and sialate-O-acetylesterase activities in childhood acute lymphoblastic leukemia

Abstract

Enhanced expression of 9-O-acetylated sialoglycoproteins (Neu5,9Ac₂-GPs) and 9-O-acetylated disialoganglioside (9-OAcGD3) was observed on lymphoblasts of childhood acute lymphoblastic leukemia (ALL). Sialate-O-acetyltransferase (SOAT) and sialate-O-acetylesterase (SIAE) are the two main enzymes responsible for the quantity of the O-acetyl ester groups on sialic acids. We have earlier shown an enhanced level of SOAT activity, capable of transferring acetyl groups to sialic acids (Sia) of glycoconjugates in the microsomes of lymphoblasts of these children. We further observed a decreased SIAE activity both in lysosomal and cytosolic fractions of ALL-cell lines and primary cells from bone marrow of patients compared to peripheral blood mononuclear cells from healthy donors, which preferentially hydrolyse O-acetyl groups at C-9 of Sia. The level of O-acetylated Sias in the cytosolic and lysosomal fractions showed a good correlation with SIAE activity in the corresponding fractions. The apparent Km values for SIAE in the lysosomal and cytosolic fractions from lymphoblasts of ALL patients are 0.38 and 0.39 mM respectively. These studies demonstrate that both SIAE and SOAT activities seem to be responsible for the enhanced level of Neu5,9Ac₂ in lymphoblasts, which is a hall mark in ALL. This was subsequently confirmed by using an ELISA that also demonstrated a steady decline of SOAT activities even in cell lysates of lymphoblasts during successful chemotherapy, like radioactive methods shown earlier.