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Novel tumor antigens elicit anti-tumor humoral immune reactions in a subset of patients with polycythemia vera.

ABSTRACT: We attempted to determine whether the immune reactions elicited by aberrantly expressed testis antigens contribute to the beneficial responses to interferon (IFN)-alpha therapy and other therapies in patients with polycythemia vera (PV). We screened a human testis cDNA library using SEREX (serological analysis of tumor antigens by screening an expression cDNA library with sera from three patients with PV who had undergone IFN-alpha-induced or other therapeutics-induced remission). We identified two novel PV associated tumor antigens, PV65 (eIF-2alpha) and PV13 (protamine 2). These 2 antigens elicited IgG antibody reactions in a subset of PV patients but not in healthy donors, suggesting that they are authentic tumor antigens. Increased phosphorylation of PV65 in response to stimulation of IFN-alpha, and upregulation of PV13 in tumor cells might enhance their abilities in elicitation of immune reactions in patients. These findings provide new insights into the mechanism underlying the regulation of the self-antigen repertoire in eliciting anti-tumor immune reactions in patients with polycythemia vera, and suggest their potential as the targets of novel immunotherapy.

SUBMITTER: Xiong Z

PROVIDER: S-EPMC2637448 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature

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Novel tumor antigens elicit anti-tumor humoral immune reactions in a subset of patients with polycythemia vera.

Xiong Zeyu Z Yan Yan Y Liu Enli E Silver Richard T RT Verstovsek Srdan S Yang Fan F Wang Hong H Prchal Josef J Yang Xiao-Feng XF

Clinical immunology (Orlando, Fla.) 20061117 3

We attempted to determine whether the immune reactions elicited by aberrantly expressed testis antigens contribute to the beneficial responses to interferon (IFN)-alpha therapy and other therapies in patients with polycythemia vera (PV). We screened a human testis cDNA library using SEREX (serological analysis of tumor antigens by screening an expression cDNA library with sera from three patients with PV who had undergone IFN-alpha-induced or other therapeutics-induced remission). We identified ...[more]

PMID: 17113348

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Project description:BackgroundPolycythemia vera is the ultimate phenotypic consequence of the V617F mutation in Janus kinase 2 (encoded by JAK2), but the extent to which this mutation influences the behavior of the involved CD34+ hematopoietic stem cells is unknown.MethodsWe analyzed gene expression in CD34+ peripheral-blood cells from 19 patients with polycythemia vera, using oligonucleotide microarray technology after correcting for potential confounding by sex, since the phenotypic features of the disease differ between men and women.ResultsMen with polycythemia vera had twice as many up-regulated or down-regulated genes as women with polycythemia vera, in a comparison of gene expression in the patients and in healthy persons of the same sex, but there were 102 genes with differential regulation that was concordant in men and women. When these genes were used for class discovery by means of unsupervised hierarchical clustering, the 19 patients could be divided into two groups that did not differ significantly with respect to age, neutrophil JAK2 V617F allele burden, white-cell count, platelet count, or clonal dominance. However, they did differ significantly with respect to disease duration; hemoglobin level; frequency of thromboembolic events, palpable splenomegaly, and splenectomy; chemotherapy exposure; leukemic transformation; and survival. The unsupervised clustering was confirmed by a supervised approach with the use of a top-scoring-pair classifier that segregated the 19 patients into the same two phenotypic groups with 100% accuracy.ConclusionsRemoving sex as a potential confounder, we identified an accurate molecular method for classifying patients with polycythemia vera according to disease behavior, independently of their JAK2 V617F allele burden, and identified previously unrecognized molecular pathways in polycythemia vera outside the canonical JAK2 pathway that may be amenable to targeted therapy. (Funded by the Department of Defense and the National Institutes of Health.).

Dataset Information

Novel tumor antigens elicit anti-tumor humoral immune reactions in a subset of patients with polycythemia vera.

Publications

Novel tumor antigens elicit anti-tumor humoral immune reactions in a subset of patients with polycythemia vera.

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