Multiple Roles of Glycans in Hematological Malignancies

Abstract

The three types of blood cells (red blood cells for carrying oxygen, white blood cells for immune protection, and platelets for wound clotting) arise from hematopoietic stem/progenitor cells in the adult bone marrow, and function in physiological regulation and communication with local microenvironments to maintain systemic homeostasis. Hematological malignancies are relatively uncommon malignant disorders derived from the two major blood cell lineages: myeloid (leukemia) and lymphoid (lymphoma). Malignant clones lose their regulatory mechanisms, resulting in production of a large number of dysfunctional cells and destruction of normal hematopoiesis. Glycans are one of the four major types of essential biological macromolecules, along with nucleic acids, proteins, and lipids. Major glycan subgroups are N-glycans, O-glycans, glycosaminoglycans, and glycosphingolipids. Aberrant expression of glycan structures, resulting from dysregulation of glycan-related genes, is associated with cancer development and progression in terms of cell signaling and communication, tumor cell dissociation and invasion, cell-matrix interactions, tumor angiogenesis, immune modulation, and metastasis formation. Aberrant glycan expression occurs in most hematological malignancies, notably acute myeloid leukemia, myeloproliferative neoplasms, and multiple myeloma, etc. Here, we review recent research advances regarding aberrant glycans, their related genes, and their roles in hematological malignancies. Our improved understanding of the mechanisms that underlie aberrant patterns of glycosylation will lead to development of novel, more effective therapeutic approaches targeted to hematological malignancies.

Oligosaccharyltransferase: A Gatekeeper of Health and Tumor Progression

“…As a consequence, tumor cells express aberrant N-glycans, which have been shown to be associated with malignancy and poor prognosis. The correlation between tumor progression and the terminal modification of N-glycans has long been an extensive focus of basic and clinical research studies in glycobiology and have been sophisticatedly reviewed elsewhere [6,7,8,9,10,11,12,13,14,15,16]. In contrast, the association of OST with tumor progression has only recently been explored.…”

B4GALT1 Is a New Candidate to Maintain the Stemness of Lung Cancer Stem Cells

“…Surprisingly, among the top 10% genes exhibiting the most significant transcript abundance shift (Table S1), we found the gene B4GALT1. Notably, B4GALT1 protein has been previously associated with multi-drug-resistant cell phenotype in human leukemia [52] and other haematological malignancies [53,54]. On the other side, genes significantly downregulated were associated with MYC and E2F target genes (Figure S2).…”

Immunoaffinity Capillary Electrophoresis in the Era of Proteoforms, Liquid Biopsy and Preventive Medicine: A Potential Impact in the Diagnosis and Monitoring of Disease Progression

“…More recently, it was reported that small RNAs which are modified with N-glycans are displayed on the surface of living cells [227]. Many malignancies are characterized by abnormal glycosylation, which is commonly associated with the oncogenesis and cancer progression [224][225][226][228][229][230][231][232][233][234][235][236][237][238]. Furthermore, persistent non-malignant inflammatory conditions cause continual upregulation of enzymes that promote numerous molecular changes, including glycosylation as well [228][229][230][231][232][233][234][235][236][237].…”