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

TY - JOUR

T1 - 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

AU - Biedermann, Bjoern

AU - Gil, Diana

AU - Bowen, David T.

AU - Crocker, Paul R.

PY - 2007/2

Y1 - 2007/2

N2 - 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.

AB - 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.

KW - Acute Disease

KW - Antigens, CD

KW - Antigens, Differentiation, Myelomonocytic

KW - Flow Cytometry

KW - Hematopoietic Stem Cells

KW - Humans

KW - Lectins

KW - Leukemia, Myeloid

KW - Sialic Acid Binding Ig-like Lectin 3

KW - Sialic Acid Binding Immunoglobulin-like Lectins

KW - Tumor Markers, Biological

U2 - 10.1016/j.leukres.2006.05.026

DO - 10.1016/j.leukres.2006.05.026

M3 - Article

C2 - 16828866

SN - 0145-2126

VL - 31

SP - 211

EP - 220

JO - Leukemia Research

JF - Leukemia Research

IS - 2

ER -