Analysis of the CD33-related siglec family reveals that Siglec-9 is an endocytic receptor expressed on subsets of acute myeloid leukemia cells and absent from normal hematopoietic progenitors.
CD33 (Siglec-3) is expressed on most acute myeloid leukemia (AML) cells and is currently being exploited as a therapeutic target. The purpose of this study was to investigate the expression pattern and potential utility of the seven recently described CD33-related siglecs as markers in AML. Besides CD33, Siglec-9 was the most highly expressed, particularly on AML cells with features of monocytic differentiation that also expressed Siglecs-5 and -7. Siglec-9 was absent from normal bone marrow myeloid progenitors but present on monocytic precursors. Using primary AML cells or transfected rat basophilic leukemia cells, Siglec-9 mediated rapid endocytosis of anti-Siglec-9 mAb. In contrast to CD33 and Siglec-5, levels of soluble Siglec-9 were low or undetectable in bone marrow plasma from AML patients and serum from normal donors. These features suggest that Siglec-9 provides not only a useful marker for certain subsets of AML, but also a potential therapeutic target.
Biedermann
Bjoern
B
Division of Cell Biology and Immunology, School of Life Sciences, University of Dundee, UK.
Gil
Diana
D
Bowen
David T
DT
Crocker
Paul R
PR
D000208:Acute Disease; D015703:Antigens, CD / Q000032:analysis* / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis* / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis; D005434:Flow Cytometry / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D037102:Lectins / Q000032:analysis* / Q000096:biosynthesis; D007951:Leukemia, Myeloid / Q000276:immunology*; D063268:Sialic Acid Binding Ig-like Lectin 3; D063265:Sialic Acid Binding Immunoglobulin-like Lectins
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; C571163:CD33 protein, human; D037102:Lectins; C114531:SIGLEC5 protein, human; C402206:SIGLEC7 protein, human; C412227:SIGLEC9 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3; D063265:Sialic Acid Binding Immunoglobulin-like Lectins