Complement Receptor 1 (CR1) Expression in Chronic Myeloid Leukemia

Abstract

The complement receptor 1 (CR1), also called CD35, is a polymorphic glycoprotein which mediates a variety of neutrophil functions, including phagocytosis and, probably, tumor cell cytotoxicity. The role played by this molecule in chronic myeloid leukemia (CML) is not yet well understood. CML frequently shows a marked decrease of CR1 antigens on both the neutrophil population and myeloid precursors. This reduced expression appears to be related to disease activity, since patients at more advanced clinical stages, as well as those who develop blastic crisis, have been found to express the lowest levels of CR1 antigens. At the onset of the disease low CR1 expression on CML neutrophils seems to be associated with a higher risk of blastic transformation. Furthermore, CML neutrophils deficient in CR1 lack the ability to respond to PMA stimulation, suggesting a failure in CR1 granular storage. In patients lacking CR1, the number of receptors increased to normal levels following exposure of CML cells to therapeutic concentrations of recombinant alpha interferon.

The role played by the CR1 molecule in sustaining neutrophil-mediated tumor cell cytotoxicity has yet to be definitively proved; studies performed by our group are relevant here, since complete suppression of tumor lysis following receptor neutralization by anti CR1 monoclonal antibodies was demonstrated in a large number of normal and CML individuals. In CML patients, the evidence of a direct relationship between lytic activity and antigen receptor levels seems to further support the involvement of CR1 molecules in tumor cell lysis function. Whether CR1 has a causative role in CML has still to be demonstrated, since various biological studies seem to support the theory that CR1 deficiency may represent a secondary event. Further studies are needed in order to clarify this intriguing point, and to evaluate CR1 expression during normal and leukemic myeloid differentiation pathways.

Key Words:

• Complement receptor 1
• CML
• prognosis
• neutrophil
• interferon
• myeloid precursors
• blastic crisis
• stem cells
• functional activities