Pre-B acute lymphoblastic leukemia expresses cell surface nucleolin as a 9-O-acetylated sialoglycoprotein

• Published in: Scientific reports Vol. 8; no. 1; pp. 17174 - 13
• Main Authors: Joo, Eun Ji, Wasik, Brian R, Parrish, Colin, Paz, Helicia, Mϋhlenhoff, Martina, Abdel-Azim, Hisham, Groffen, John, Heisterkamp, Nora
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21-11-2018; Nature Publishing Group
• Subjects: 13; 13/106; 13/31; 14; 14/1; 631/45/221; 631/67/1990/283/2125; 82; 82/1; 82/16; 82/29; 82/83; Acute lymphoblastic leukemia; Aptamers; Cancer; Cell proliferation; Cell surface; Cells, Cultured; Chemotherapy; Glycoproteins; Humanities and Social Sciences; Humans; Internalization; Lectins; Leukemia; Localization; Lymphatic leukemia; Lymphocytes B; Membrane Proteins - analysis; multidisciplinary; Nucleolin; Phosphoproteins - analysis; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Precursor Cells, B-Lymphoid - chemistry; RNA-Binding Proteins - analysis; Science; Science (multidisciplinary); Sialoglycoproteins - analysis; Therapeutic applications; Vincristine; Porcine Torovirus; Sialoglycoprotein; Sialidase Treatment; Specific Glycan Structures; Sialylation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-33873-2

Precursor B acute lymphoblastic leukemias (pre-B ALLs) abnormally express a specific glycan structure, 9-
O-
acetylated sialic acid (9
-O-
Ac-Sia), on their cell surface, but glycoproteins that carry this modification have not been identified. Using three different lectins that specifically recognize this structure, we establish that nucleolin (NCL), a protein implicated in cancer, contains 9-
O
-Ac-Sia. Surprisingly, antibodies against the glycolipid 9
-O-
Ac-Sia GD3 also detected 9
-O-
Ac-Sia NCL. NCL is present on the surface of pre-B ALL cells as a sialoglycoprotein that is partly 9-
O
-acetylated and conversely, 9-
O
-Ac-Sia-containing structures other than NCL are present on these cells as well. Interestingly, NCL and the 9
-O-
Ac-Sia signal had less co-localization on normal pre-B cells. We also investigated regulation of NCL on the cell surface and found that sialidase treatment increased the percentage of cells positive for cell surface NCL, suggesting that sialylation of NCL promotes internalization. Treatment of pre-B ALL cells with the chemotherapy drug vincristine also increased the percentage of cells with surface NCL and correlated with increased 9
-O-
Ac-Sia expression. All tested leukemia cells including primary samples expressed NCL, suggesting it as a possible therapeutic target. We confirmed this by showing inhibition of cell proliferation in some pre-B ALLs by exposure to a NCL-specific aptamer AS1411.