Biomaterial Database

Molecular Basis and Role of Siglec-7 Ligand Expression on Chronic Lymphocytic Leukemia B Cells. 2022

Lan-Yi Chang, and Suh-Yuen Liang, and Shao-Chia Lu, and Huan Chuan Tseng, and Ho-Yang Tsai, and Chin-Ju Tang, and Marcelia Sugata, and Yi-Ju Chen, and Yu-Ju Chen, and Shang-Ju Wu, and Kuo-I Lin, and Kay-Hooi Khoo, and Takashi Angata

Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.

Siglec-7 (sialic acid-binding immunoglobulin-like lectin 7) is an immune checkpoint-like glycan recognition protein on natural killer (NK) cells. Cancer cells often upregulate Siglec ligands to subvert immunosurveillance, but the molecular basis of Siglec ligands has been elusive. In this study, we investigated Siglec-7 ligands on chronic lymphocytic leukemia (CLL) B cells. CLL B cells express higher levels of Siglec-7 ligands compared with healthy donor B cells, and enzymatic removal of sialic acids or sialomucins makes them more sensitive to NK cell cytotoxicity. Gene knockout experiments have revealed that the sialyltransferase ST6GalNAc-IV is responsible for the biosynthesis of disialyl-T (Neu5Acα2-3Galβ1-3[Neu5Acα2-6]GalNAcα1-), which is the glycotope recognized by Siglec-7, and that CD162 and CD45 are the major carriers of this glycotope on CLL B cells. Analysis of public transcriptomic datasets indicated that the low expression of GCNT1 (encoding core 2 GlcNAc transferase, an enzyme that competes against ST6GalNAc-IV) and high expression of ST6GALNAC4 (encoding ST6GalNAc-IV) in CLL B cells, together enhancing the expression of the disialyl-T glycotope, are associated with poor patient prognosis. Taken together, our results determined the molecular basis of Siglec-7 ligand overexpression that protects CLL B cells from NK cell cytotoxicity and identified disialyl-T as a potential prognostic marker of CLL.

UI	MeSH Term	Description	Entries
D007694	Killer Cells, Natural	Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.	NK Cells,Natural Killer Cells,Cell, NK,Cell, Natural Killer,Cells, NK,Cells, Natural Killer,Killer Cell, Natural,NK Cell,Natural Killer Cell
D008024	Ligands	A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)	Ligand
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001402	B-Lymphocytes	Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.	B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent
D015451	Leukemia, Lymphocytic, Chronic, B-Cell	A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.	B-Cell Leukemia, Chronic,B-Lymphocytic Leukemia, Chronic,Chronic Lymphocytic Leukemia,Leukemia, B-Cell, Chronic,Leukemia, Lymphocytic, Chronic,Lymphocytic Leukemia, Chronic, B-Cell,Lymphoma, Small Lymphocytic,B-Cell Chronic Lymphocytic Leukemia,B-Cell Malignancy, Low-Grade,Diffuse Well-Differentiated Lymphocytic Lymphoma,Disrupted In B-Cell Malignancy,Leukemia, B Cell, Chronic,Leukemia, Chronic Lymphatic,Leukemia, Chronic Lymphocytic,Leukemia, Chronic Lymphocytic, B-Cell,Leukemia, Lymphoblastic, Chronic,Leukemia, Lymphocytic, Chronic, B Cell,Lymphoblastic Leukemia, Chronic,Lymphocytic Leukemia, Chronic,Lymphocytic Leukemia, Chronic, B Cell,Lymphocytic Lymphoma,Lymphocytic Lymphoma, Diffuse, Well Differentiated,Lymphocytic Lymphoma, Diffuse, Well-Differentiated,Lymphocytic Lymphoma, Well Differentiated,Lymphocytic Lymphoma, Well-Differentiated,Lymphoma, Lymphocytic,Lymphoma, Lymphocytic, Diffuse, Well Differentiated,Lymphoma, Lymphocytic, Diffuse, Well-Differentiated,Lymphoma, Lymphocytic, Well Differentiated,Lymphoma, Lymphocytic, Well-Differentiated,Lymphoma, Lymphoplasmacytoid, CLL,Lymphoma, Small Lymphocytic, Plasmacytoid,Lymphoma, Small-Cell,Lymphoplasmacytoid Lymphoma, CLL,Small-Cell Lymphoma,B Cell Chronic Lymphocytic Leukemia,B Cell Leukemia, Chronic,B Cell Malignancy, Low Grade,B Lymphocytic Leukemia, Chronic,B-Cell Leukemias, Chronic,B-Cell Malignancies, Low-Grade,B-Lymphocytic Leukemias, Chronic,CLL Lymphoplasmacytoid Lymphoma,CLL Lymphoplasmacytoid Lymphomas,Chronic B-Cell Leukemia,Chronic B-Cell Leukemias,Chronic B-Lymphocytic Leukemia,Chronic B-Lymphocytic Leukemias,Chronic Lymphatic Leukemia,Chronic Lymphatic Leukemias,Chronic Lymphoblastic Leukemia,Chronic Lymphoblastic Leukemias,Chronic Lymphocytic Leukemias,Diffuse Well Differentiated Lymphocytic Lymphoma,Disrupted In B Cell Malignancy,Leukemia, Chronic B-Cell,Leukemia, Chronic B-Lymphocytic,Leukemias, Chronic B-Cell,Leukemias, Chronic B-Lymphocytic,Leukemias, Chronic Lymphatic,Leukemias, Chronic Lymphoblastic,Low-Grade B-Cell Malignancies,Low-Grade B-Cell Malignancy,Lymphatic Leukemia, Chronic,Lymphatic Leukemias, Chronic,Lymphoblastic Leukemias, Chronic,Lymphocytic Leukemias, Chronic,Lymphocytic Lymphoma, Small,Lymphocytic Lymphomas,Lymphocytic Lymphomas, Small,Lymphocytic Lymphomas, Well-Differentiated,Lymphoma, CLL Lymphoplasmacytoid,Lymphoma, Small Cell,Lymphoma, Well-Differentiated Lymphocytic,Lymphomas, CLL Lymphoplasmacytoid,Lymphomas, Lymphocytic,Lymphomas, Small Lymphocytic,Lymphomas, Small-Cell,Lymphomas, Well-Differentiated Lymphocytic,Lymphoplasmacytoid Lymphomas, CLL,Malignancies, Low-Grade B-Cell,Malignancy, Low-Grade B-Cell,Small Cell Lymphoma,Small Lymphocytic Lymphoma,Small Lymphocytic Lymphomas,Small-Cell Lymphomas,Well-Differentiated Lymphocytic Lymphoma,Well-Differentiated Lymphocytic Lymphomas
D063265	Sialic Acid Binding Immunoglobulin-like Lectins	A family of SIALIC ACID binding proteins found in vertebrate species. They are transmembrane proteins which act as cell surface receptors for a variety of sialylated GLYCOCONJUGATES. While a subset of siglec protein subtypes are evolutionarily conserved between mammalian species, there are many others that are species specific.	Sialic Acid Binding Ig-like Lectin,Sialic Acid-binding Hemagglutinin,Siglec,Siglecs,Hemagglutinin, Sialic Acid-binding,Sialic Acid Binding Ig like Lectin,Sialic Acid Binding Immunoglobulin like Lectins,Sialic Acid binding Hemagglutinin