Blood, Vol. 92 No. 12 (December 15), 1998:
pp. 4764-4770
Prevalence of Antibodies Against Proteins Derived From
Leukemia Cells in Patients With Chronic Myeloid Leukemia
Min Ling,
Yue-Jin Wen, and
Seah H. Lim
From the Department of Haematology, University of Wales College of
Medicine, Cardiff, UK.
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.
