Engagement of p75/AIRM1 or CD33 inhibits the proliferation of normal or leukemic myeloid cells.
P75/AIRM1 is a recently identified surface molecule that belongs to the sialoadhesin family and displays homology with the myeloid cell antigen CD33. In lymphoid cells, p75/AIRM1 is confined to natural killer cells and mediates inhibition of their cytolytic activity. In this study, we show that p75/AIRM1 is also expressed by cells of the myelomonocytic cell lineage, in which it appears at a later stage as compared with CD33. In vitro proliferation and differentiation of cord blood-derived CD34(+) cells (induced by stem cell factor and granulocyte-macrophage colony-stimulating factor) were consistently inhibited by the addition of anti-p75/AIRM1 mAb. Engagement of CD33 led to inhibition in some experiments. A sharp decrease of cell proliferation/survival was detected in all three p75/AIRM1+ chronic myeloid leukemias analyzed when cultured in the presence of either anti-p75/AIRM1 or anti-CD33 mAbs. Thus, the present study suggests that p75/AIRM1 and CD33 may play a regulatory role in normal myelopoiesis and may be viewed as suitable target molecules to counteract the proliferation/survival of chronic myeloid leukemias.
Vitale
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C
Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova, Italy.
Romagnani
C
C
Falco
M
M
Ponte
M
M
Vitale
M
M
Moretta
A
A
Bacigalupo
A
A
Moretta
L
L
Mingari
M C
MC
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D018952:Antigens, CD34 / Q000302:isolation & purification; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage; D046508:Culture Techniques / Q000379:methods; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D017228:Hepatocyte Growth Factor; D006801:Humans; D007152:Immunologic Capping; D018189:Immunomagnetic Separation; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D009000:Monocytes / Q000166:cytology*; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D063268:Sialic Acid Binding Ig-like Lectin 3
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D011971:Receptors, Immunologic; D063268:Sialic Acid Binding Ig-like Lectin 3; C121772:adhesion inhibitory receptor molecule 1; D017228:Hepatocyte Growth Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor