Immune reactivity against Janus Kinase 2 mutation V617F in Polycythemia Vera Patients
Abstract:Polycythemia Vera (PV) is a part of a group of Philadelphia Chromosome negative myeloproliferative diseases, in which an acquired Valine to Phenylalanine mutation in exon 12 of Janus Kinase II gene in a hematopoietic stem cell yields malignant clonal hyperproliferation leading to increased morbidity and mortality caused by trombosis, bone marrow fibrosis and severe Acute Myeloid Leukemia. The mutation is found in more that 90% of PV-patients and in ∼20% of chronic neutrophilic leukaemia and atypical chronic myeloid leukaemia. The JAK II V617F mutation represents an obvious target for cancer immune therapy. The overall purpose of this study is to investigate whether patients harbouring this mutation elicit a spontaneous T cell response against mutated JAK II Kinase and subsequently if reacting JAK II specific T cells are capable of killing target cells. Thus, we have predicted peptides at and surrounding the V617F mutation capable of binding to HLA molecules (included HLA molecules are HLA A2, A3 and A24 covering about 80% of Caucasian population). These peptides are used to study peripheral blood lymphocytes from PV patients for the presence of T cells capable of recognizing the predicted peptides in the context of the appropriate HLA molecule. The frequency and phenotype of reacting cells in patients expressing these HLA molecules will be analysed in order to examine a possible correlation between immune reactivity and disease progress. The ultimate goal is to prepare the platform for a clinical vaccination trial targeting the JAK II mutation.
Preliminary results: 60 polycythemia vera patients harbouring the mutation have been HLA-typed and their T cells tested in Elispots with HLA matched peptides. Two medium sized and a weak response have been detected. These preliminary results suggest the existence of an immune response against JAK II V617F.
Document Type: Abstract
Affiliations: 1: Hæmatologisk ambulatorium, Herlev Universitets Hospital, Hæmatologisk Afdeling, Herlev Ringvej 75, 2730 Herlev 2: Center for Cancer ImmunTerapi (CCIT), Herlev Universitets Hospital, Hæmatologisk Afdeling, Herlev Ringvej 75, 2730 Herlev
Publication date: 2008-05-01