Academic Journal
Restricted human CD45 isoglycoforms serve as functional E-selectin ligands and delineate hematopoietic maturity.
| Τίτλος: | Restricted human CD45 isoglycoforms serve as functional E-selectin ligands and delineate hematopoietic maturity. |
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| Συγγραφείς: | Ales E; Department of Translational Medicine and Translational Glycobiology Institute, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, USA., Sackstein R; Department of Translational Medicine and Translational Glycobiology Institute, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, USA. Electronic address: sackstein@fiu.edu. |
| Πηγή: | The Journal of biological chemistry [J Biol Chem] 2025 Aug; Vol. 301 (8), pp. 110431. Date of Electronic Publication: 2025 Jul 01. |
| Τύπος έκδοσης: | Journal Article; Research Support, N.I.H., Extramural |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| Ιατρικοί όροι (MeSH): | Leukocyte Common Antigens*/metabolism , Leukocyte Common Antigens*/genetics , Leukocyte Common Antigens*/chemistry , Leukemia, Myeloid, Acute*/metabolism , Leukemia, Myeloid, Acute*/pathology , Leukemia, Myeloid, Acute*/genetics , E-Selectin*/metabolism , E-Selectin*/genetics , Hematopoietic Stem Cells*/metabolism , Hematopoietic Stem Cells*/cytology , Hematopoietic Stem Cells*/pathology, Protein Isoforms/metabolism ; Protein Isoforms/genetics ; Humans ; Ligands |
| Περίληψη: | CD45 is the most abundant glycoprotein on the surface of all nucleated hematopoietic-lineage cells, comprising multiple isoforms generated by alternative splicing of three exons ("A," "B," and "C"), which are exquisitely restricted across hematopoietic development. Despite the ubiquitous expression of CD45 on hematopoietic cells, its function(s) remain rather obscure. Here, we report that discrete CD45 isoforms expressed uniquely by immature human hematopoietic cells are distinguished as functional glycoforms ("isoglycoforms") that bind E-selectin. Moreover, our studies indicate that "CD45RA," a marker of human acute myeloid leukemia (AML) cells, identifies a distinct isoglycoform of CD45 containing all splice exon-encoded peptides. This isoglycoform, "CD45RABC-E," is directly upregulated by AML cells and demarcates these malignant cells from mature human leukocytes and the native human hematopoietic stem cell. Further analyses revealed that treatment-resistant AML highly expresses CD45RABC-E. Our findings thus unveil heretofore unrecognized functions of CD45 and define a novel CD45 isoglycoform that delineates AML cells from life-sustaining human hematopoietic cells. (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. |
| Grant Information: | U01 CA225730 United States CA NCI NIH HHS |
| Contributed Indexing: | Keywords: CD15s; CD45; CD45 isoform; E-selectin; E-selectin ligand; isoglycoform; sLeX; sialyl Lewis X; translational glycobiology |
| Substance Nomenclature: | EC 3.1.3.48 (Leukocyte Common Antigens) 0 (E-Selectin) EC 3.1.3.48 (PTPRC protein, human) 0 (Ligands) 0 (Protein Isoforms) |
| Entry Date(s): | Date Created: 20250703 Date Completed: 20250903 Latest Revision: 20260225 |
| Update Code: | 20260225 |
| PubMed Central ID: | PMC12336693 |
| DOI: | 10.1016/j.jbc.2025.110431 |
| PMID: | 40609795 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1083-351X |
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| DOI: | 10.1016/j.jbc.2025.110431 |