Prevalence of antibodies against proteins derived from leukemia cells in patients with chronic myeloid leukemia.
Although various studies supported the notion that leukemia cells in chronic myeloid leukemia (CML) may be recognized by the immune system, direct evidence showing the immunogenicity in vivo of proteins derived from the leukemia cells is lacking. In this study, we have constructed an expression cDNA library from the leukemia cells of a patient with CML and used the autologous serum to screen for high-titer IgG antibodies directed at the leukemia-derived proteins. We isolated eight distinct clones from the library, suggesting that multiple immune responses were elicited in the autologous host. Sequence analysis showed high degrees of homology to known gene sequences in six of the eight clones. Neither bcr-abl nor proteinase 3 sequences were isolated. Using Northern blot analysis, seven of the eight clones showed ubiquitous expression in normal bone marrow, leukemia cell lines, fresh leukemia cells, and normal tissues. However, clone no. 4 showed restricted mRNA expression, being only detected in some fresh leukemia cells, K562 cells, and normal testicular RNA. Using bacterial lysates in dot blot analysis, a panel of sera from normal individuals and patients with CML and other hematological malignancies were screened for high-titer antibodies against these eight clones. There were, among the CML patients, signficantly higher prevalence of antibodies against seven of the eight clones. They were observed even after omitting from the analysis patients with multiple myeloma whose associated immune paresis may impair immune responses to these proteins. Interestingly, antibodies against these proteins were also detected in a small number of normal individuals. Although the precise clinical significance of our findings remains to be determined, this study provides evidence in support of the potential immunogenicity of leukemia-derived proteins in the autologous host. It also provides basis for further investigations to characterize these proteins, especially clone no. 4, and determine their potential for immune targeting in CML.
Ling
M
M
Department of Haematology, University of Wales College of Medicine, Cardiff, UK.
Wen
Y J
YJ
Lim
S H
SH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics; D015152:Blotting, Northern; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis; D005260:Female; D015870:Gene Expression; D015723:Gene Library; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000906:Antibodies; D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D009363:Neoplasm Proteins; D012333:RNA, Messenger