Expression of Leukemia-Associated Antigens (LAA) in Patients with Acute Myelogenous Leukemia (AML).

Abstract

Introduction: Immunotherapeutic approaches may be effective additional options to conventional chemotherapy and stem cell transplantation regimens in the treatment of patients with acute myelogenous leukaemia (AML). Without eliciting significant side effects they may help to prolong disease-free survival or at least may delay the time to progression. Immuniotherapeutic strategies comprise vaccination with professional antigen-presenting dendritic cells or transfusion of T-cells with specific anti-leukemic activity. Leukemia-associated antigens are useful targets as they are expressed predominantly in the malignant cells and constitutively not detectable in normal tissue, or as they are at least significantly overexpressed in the leukemic blasts. To determine potential targets for specific immunotherapy in our patients with AML, we started to analyze the antigen profiles of these patients' leukemia cells using the previously characterized leukemia-associated antigens survivin, WT1, and proteinase-3 (with the HLA-A2-specific nonameric peptide PR-1), and c-Ski, an antigen recently found to be predominantly but not exclusively overexpressed in AML with deletion or monosomy of chromosome 7, indicating a poor prognosis.Methods: The mRNA expression of the above mentioned antigens was examined by conventional RT-PCR. Blasts from patients with AML were collected at diagnosis or at first relapse from peripheral blood and analyzed.Results: The antigen expression pattern in comparison to the AML cell lines HL-60 and K-562 is shown in Table 1.Conclusions: Although treatment of AML patients became more effective during the last decades, high relapse rates contribute to the poor prognosis of the disease. Additional therapeutic strategies are needed to help and prevent disease relapse. Immunotherapy directed to LAA might elicit specific CTL responses effectively eliminating minimal residual disease. Using the LAA profile shown above, we should be able to determine at least one antigen in each patient with AML to serve as a target for individual specific immunotherapy with antigen-loaded autologous dendritic cells or /and specific autologous T-cells.Table 1:Expression pattern of the LAA survivin, WT1, proteinase-3 und c-Ski in AML cell lines HL-60 and K-562, and in seven patients with AML. +/++/+++ positive, - negative, n.d. not determined yet-actinβsurvivinWT-1PRO3c-skiHL-60++++++++++++K-562+++++++−−B.R.++++++++++++++B.G.+++−+++−B.C.+++−n.d.n.d.n.d.E.B.+++−−n.d.n.d.E.E.++++++++++++S.T.++++++++++++V.B.++++++n.d.n.d.n.d.