Expression of complement regulatory proteins CR1, DAF, MCP and CD59 in haematological malignancies.
Host cells are protected from the lytic effect of the complement system by complement regulatory proteins. This study was designed to investigate the expression of complement regulatory proteins on leukemic blasts which may be susceptible to the lytic effects of the complement system in the circulation. The surface expressions of complement regulatory proteins, complement receptor 1 (CR1, CD35), decay accelerating factor (DAF, CD55), and homologous restriction factor 20 (HRF20, CD59), on peripheral blood and bone marrow blasts were evaluated by using flow cytometry in 16 acute myeloblastic leukemia (AML), 16 acute lymphoblastic leukemia (ALL), 4 chronic lymphocytic leukemia (CLL), 3 chronic myelocytic leukemia (CML) patients and control granulocytes and lymphocytes obtained from 15 healthy volunteers. mRNA expression was investigated by Northern blot analysis. mRNA abundances were calculated after normalization according to 28s rRNA. Surface expressions of CRI and DAF were marginally (p = 0.08 and p = 0.08, respectively) lower in AML, and DAF expression was significantly lower (p=0.0008) in ALL patients in comparison to their normal counterparts. Except from a slight increase that is detected for CD59 in CML patients (p=0.06), there was no significant difference between the surface expressions of CD59 in any of the groups studied. Densitometric analysis of autoradiographs obtained from Northern blots revealed that in AML patients, CR1 mRNA expression were 5.5-fold lower than controls (p=0.06), while DAF mRNA expression was significantly higher (p=0.0046). Furthermore, the mRNA expression of CRI in ALL patients was found significantly lower than in the control group (p = 0.0419). None of the values obtained from the other groups were significantly different from each other. These results suggest that leukemic blasts are protected from the lytic attack of the complement system at all levels, since all of the complement membrane regulatory proteins were expressed in all leukemia types (although at lower amounts in some cases), and it is also possible to use CRI and DAF as differentiation markers in acute leukemias.
Guc
D
D
Basic Oncology Department, Oncology Institute, Hacettepe University, Ankara, Turkey.
Canpinar
H
H
Kucukaksu
C
C
Kansu
E
E
D015703:Antigens, CD / Q000097:blood / Q000235:genetics*; D001752:Blast Crisis / Q000097:blood / Q000473:pathology; D001854:Bone Marrow Cells / Q000473:pathology*; D018958:CD55 Antigens / Q000097:blood / Q000235:genetics*; D018957:CD59 Antigens / Q000097:blood / Q000235:genetics*; D006098:Granulocytes / Q000166:cytology; D006801:Humans; D007938:Leukemia / Q000097:blood / Q000235:genetics* / Q000473:pathology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000235:genetics / Q000473:pathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000235:genetics / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000235:genetics / Q000473:pathology; D008214:Lymphocytes / Q000166:cytology; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D017463:Receptors, Complement 3b / Q000097:blood / Q000235:genetics*; D012016:Reference Values; D014158:Transcription, Genetic
D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D017463:Receptors, Complement 3b