Identification of the CD33-related Siglec receptor, Siglec-5 (CD170), as a useful marker in both normal myelopoiesis and acute myeloid leukaemias.
Sialic acid-binding immunoglobulin-like lectin (Siglec)-5 or CD170 is a CD33-related receptor, containing cytoplasmic immune receptor-based tyrosine signalling motifs, that has previously been reported to be myeloid-specific like CD33 and thus may be useful in the characterization of both normal and malignant haemopoiesis. This study showed that Siglec-5 had a distinct expression pattern to CD33 both on normal myeloid cells and in acute myeloid leukaemia (AML). In normal bone marrow and cord blood, myeloid cells predominantly expressed Siglec-5 at the later stages of granulocytic differentiation. Siglec-5 was not expressed at significant levels by CD34+ progenitors either from bone marrow or mobilized peripheral blood. During in vitro myeloid differentiation of cord blood purified CD34+ cells, Siglec-5 was upregulated later than CD33. Siglec-5 expression remained absent or very low on cultured CD34+ cells, unlike CD33, which was present on almost all CD34+ cells by day 4. However, analysis of blasts from 23 patients with AML revealed aberrant expression of Siglec-5 with CD34 in 50% (seven of 14) of patients with CD34+ AML; 61% (14 of 23) of AML cases were positive for Siglec-5 with an increased frequency in the French-American-British subtypes M3-5 (80%) compared with M0-2 (25%). All 13 acute lymphoblastic leukaemic (ALL) samples tested, including a CD33+ ALL, were Siglec-5 negative. These results support the further evaluation of Siglec-5 antibodies in the diagnosis and monitoring of AML.
Virgo
Paul
P
Department of Immunology and Immunogenetics, North Bristol, NHS Trust, Bristol, UK.
Denning-Kendall
Patricia A
PA
Erickson-Miller
Connie L
CL
Singha
Sakon
S
Evely
Roger
R
Hows
Jill M
JM
Freeman
Sylvie D
SD
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood / Q000627:therapeutic use; D015703:Antigens, CD / Q000032:analysis* / Q000276:immunology; D018952:Antigens, CD34 / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis* / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D001854:Bone Marrow Cells / Q000276:immunology*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000276:immunology; D002648:Child; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007116:Immunization, Passive; D007231:Infant, Newborn; D037102:Lectins / Q000032:analysis* / Q000276:immunology; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000628:therapy; D008875:Middle Aged; D038042:Myelopoiesis / Q000276:immunology; D063268:Sialic Acid Binding Ig-like Lectin 3; D013234:Stem Cells / Q000276:immunology
D000906:Antibodies; D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; C571163:CD33 protein, human; D037102:Lectins; C114531:SIGLEC5 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3