The contribution of the membrane-bound complement regulatory proteins CD46 and CD55 in phases of acute lymphocytic leukemia and acute myelogenous leukemia

The complement system is an essential part of the innate immunity that is involved in the elimination of pathogens as well as participating in the body's immune surveillance against cancer. However, recent findings have shown that cancerous cells can use the complement components to assist in certain hallmarks which are fundamental for tumor progression. The current study investigates the differential expression of membrane-bound complement regulatory proteins; CD46 and CD55 in leukemia. Clinical peripheral blood samples of newly diagnosed acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) patients were used to assess the changes in transcriptional expression levels of both proteins using quantitative real time PCR. Results showed that both CD46 and CD55 were significantly downregulated by 2 to 7 folds in both AML and ALL patients compared to healthy controls which is suggestive of a defense mechanism conducted by leukemic cells to overcome immune defenses. Flow cytometric analysis conducted for proteomic expression of CD46 and CD55 on cell surfaces of leukemia patients showed a reduction in expression by 1.2-fold and 2.8-fold in AML patients, respectively. Post transcriptional knockdown of both genes in leukemic cell model using customized shRNA, followed by cell viability assays showed a significant reduction in the viability of cells by 3-fold, suggesting that although the expression of both proteins could be compromised by cancerous cells to evade complement attack mechanisms, they could also be vital to the viability of cancerous cells suggesting a dual role of complement in the tumor microenvironment.