(352) Evaluation of Glycosylation Patterns and Inhibition in Acute Lymphoid Leukemia

Objective : Acute lymphoblastic leukemia (ALL) is a heterogeneous hematologic disease characterized by the proliferation of immature lymphoid cells in the bone marrow, peripheral blood, and other organs. O-linked glycosylation patterns on lymphoid cells are common modifications located on the hydroxyl groups of serine or threonine residues. Glycosylation patterns are associated with key functions including cellular uptake, regulation, and signaling of immune cells, as well as adhesion and migration. Aberrant expression of O-glycans have been associated with leukemic malignancies. The objective of this study was to perform a literature-based investigation of the influence of O-glycosylation in ALL using O-glycan inhibitors.

Methods: A literature database search for ALL glycosylation patterns and inhibitors was performed on databases which included: PubMed, Scopus, and Google Scholar. Pubmed database (1946-February 2024) was used via advanced search utilizing Boolean operator "AND" to yield 42 articles relating to leukemia and O-glycosylation, as well as 9 articles about leukemia, O-glycosylation, and inhibitors. Articles considered for review and inclusion were limited to their use of glycosylation inhibitors in Lymphoid Leukemic cell lines.

Results: The literature review confirmed the frequent observation of aberrant O-glycosylation patterns in ALL cells. The research identified three glycosylation inhibitors effective in inhibiting O-glycosylation in various lymphoid leukemia cell lines. Ac5GalNTGc was the most researched and O-glycosylation inhibition was achieved multiple lymphoid leukemia cell lines. Additionally, the literature review identified Benzyl-GalNAc and Imatinib as other effective glycosylation inhibitors showing efficacy in inhibiting O-glycosylation in lymphoblastic cells.

Conclusions: Anomalies in glycosylation patterns are linked to leukemic malignancies, rendering it an appealing target for intervention. Our research adopted an evidence-driven strategy, combing through reputable databases to compile a roster of effective O-linked glycosylation inhibitors for ALL.