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 chroni c myeloid leukemia (CML) may be recognized by the immune system, direct evi dence showing the immunogenicity in vivo of proteins derived from the leuke mia 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 autolog ous serum to screen for high-titer IgG antibodies directed at the leukemia- derived proteins. We isolated eight distinct clones from the library, sugge sting that multiple immune responses were elicited in the autologous host. Sequence analysis showed high degrees of homology to known gene sequences i n six of the eight clones. Neither bcr-abl nor proteinase 3 sequences were isolated. Using Northern blot analysis, seven of the eight clones showed ub iquitous expression in normal bone marrow, leukemia cell lines, fresh leuke mia cells, and normal tissues. However, clone no. 4 showed restricted mRNA expression, being only detected in some fresh leukemia cells, K562 cells, a nd normal testicular RNA. Using bacterial lysates in dot blot analysis, a p anel of sera from normal individuals and patients with CML and other hemato logical malignancies were screened for high-titer antibodies against these eight clones. There were, among the CML patients, significantly higher prev alence 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. In terestingly, antibodies against these proteins were also detected in a smal l number of normal individuals. Although the precise clinical significance of our findings remains to be determined, this study provides evidence in s upport of the potential immunogenicity of leukemia-derived proteins in the autologous host. It also provides basis for further investigations to chara cterize these proteins, especially clone no. 4, and determine their potenti al for immune targeting in CML. (C) 1998 by The American Society of Hematol ogy.