Immune Responses to RHAMM in Patients with Acute Myeloid Leukemia after Chemotherapy and Allogeneic Stem Cell Transplantation

Leukemic blasts overexpress immunogenic antigens, so-called leukemia-associated antigens like the receptor for hyaluronan acid-mediated motility (RHAMM). Persistent RHAMM expression and decreasing CD8+ T-cell responses to RHAMM in the framework of allogeneic stem cell transplantation or chemotherapy...

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Main Authors: R. Casalegno-Garduño, C. Meier, A. Schmitt, A. Spitschak, I. Hilgendorf, S. Rohde, C. Hirt, M. Freund, B. M. Pützer, M. Schmitt
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1155/2012/146463
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author R. Casalegno-Garduño
C. Meier
A. Schmitt
A. Spitschak
I. Hilgendorf
S. Rohde
C. Hirt
M. Freund
B. M. Pützer
M. Schmitt
author_facet R. Casalegno-Garduño
C. Meier
A. Schmitt
A. Spitschak
I. Hilgendorf
S. Rohde
C. Hirt
M. Freund
B. M. Pützer
M. Schmitt
author_sort R. Casalegno-Garduño
collection DOAJ
description Leukemic blasts overexpress immunogenic antigens, so-called leukemia-associated antigens like the receptor for hyaluronan acid-mediated motility (RHAMM). Persistent RHAMM expression and decreasing CD8+ T-cell responses to RHAMM in the framework of allogeneic stem cell transplantation or chemotherapy alone might indicate the immune escape of leukemia cells. In the present study, we analyzed the expression of RHAMM in 48 patients suffering from acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Furthermore, we correlated transcripts with the clinical course of the disease before and after treatment. Real-time quantitative reverse transcriptase polymerase chain reaction was performed from RNA of peripheral blood mononuclear cells. T cell responses against RHAMM were assessed by tetramer staining (flow cytometry) and enzyme-linked immunospot (ELISPOT) assays. Results were correlated with the clinical outcome of patients. The results of the present study showed that almost 60% of the patients were RHAMM positive; specific T-cells recognizing RHAMM could be detected, but they were nonfunctional in terms of interferon gamma or granzyme B release as demonstrated by ELISPOT assays. Immunotherapies like peptide vaccination or adoptive transfer of RHAMM-specific T cells might improve the immune response and the outcome of AML/MDS patients.
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spelling doaj-art-e106b268c77744a5a0de1fd32a9bdd022025-08-20T03:26:00ZengWileyClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/146463146463Immune Responses to RHAMM in Patients with Acute Myeloid Leukemia after Chemotherapy and Allogeneic Stem Cell TransplantationR. Casalegno-Garduño0C. Meier1A. Schmitt2A. Spitschak3I. Hilgendorf4S. Rohde5C. Hirt6M. Freund7B. M. Pützer8M. Schmitt9Department of Internal Medicine III, University of Rostock, 18057 Rostock, GermanyDepartment of Vectorology and Experimental Gene Therapy, Biomedical Research Center (BMFZ), University of Rostock, 18057 Rostock, GermanyDepartment of Internal Medicine III, University of Rostock, 18057 Rostock, GermanyDepartment of Vectorology and Experimental Gene Therapy, Biomedical Research Center (BMFZ), University of Rostock, 18057 Rostock, GermanyDepartment of Internal Medicine III, University of Rostock, 18057 Rostock, GermanyDepartment of Internal Medicine III, University of Rostock, 18057 Rostock, GermanyDepartment of Internal Medicine C, Hematology and Oncology, University of Greifswald, 17487 Greifswald, GermanyDepartment of Internal Medicine III, University of Rostock, 18057 Rostock, GermanyDepartment of Vectorology and Experimental Gene Therapy, Biomedical Research Center (BMFZ), University of Rostock, 18057 Rostock, GermanyCellular Immunotherapy, Department of Internal Medicine V, University Clinic Heidelberg, 69120 Heidelberg, GermanyLeukemic blasts overexpress immunogenic antigens, so-called leukemia-associated antigens like the receptor for hyaluronan acid-mediated motility (RHAMM). Persistent RHAMM expression and decreasing CD8+ T-cell responses to RHAMM in the framework of allogeneic stem cell transplantation or chemotherapy alone might indicate the immune escape of leukemia cells. In the present study, we analyzed the expression of RHAMM in 48 patients suffering from acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Furthermore, we correlated transcripts with the clinical course of the disease before and after treatment. Real-time quantitative reverse transcriptase polymerase chain reaction was performed from RNA of peripheral blood mononuclear cells. T cell responses against RHAMM were assessed by tetramer staining (flow cytometry) and enzyme-linked immunospot (ELISPOT) assays. Results were correlated with the clinical outcome of patients. The results of the present study showed that almost 60% of the patients were RHAMM positive; specific T-cells recognizing RHAMM could be detected, but they were nonfunctional in terms of interferon gamma or granzyme B release as demonstrated by ELISPOT assays. Immunotherapies like peptide vaccination or adoptive transfer of RHAMM-specific T cells might improve the immune response and the outcome of AML/MDS patients.http://dx.doi.org/10.1155/2012/146463
spellingShingle R. Casalegno-Garduño
C. Meier
A. Schmitt
A. Spitschak
I. Hilgendorf
S. Rohde
C. Hirt
M. Freund
B. M. Pützer
M. Schmitt
Immune Responses to RHAMM in Patients with Acute Myeloid Leukemia after Chemotherapy and Allogeneic Stem Cell Transplantation
Clinical and Developmental Immunology
title Immune Responses to RHAMM in Patients with Acute Myeloid Leukemia after Chemotherapy and Allogeneic Stem Cell Transplantation
title_full Immune Responses to RHAMM in Patients with Acute Myeloid Leukemia after Chemotherapy and Allogeneic Stem Cell Transplantation
title_fullStr Immune Responses to RHAMM in Patients with Acute Myeloid Leukemia after Chemotherapy and Allogeneic Stem Cell Transplantation
title_full_unstemmed Immune Responses to RHAMM in Patients with Acute Myeloid Leukemia after Chemotherapy and Allogeneic Stem Cell Transplantation
title_short Immune Responses to RHAMM in Patients with Acute Myeloid Leukemia after Chemotherapy and Allogeneic Stem Cell Transplantation
title_sort immune responses to rhamm in patients with acute myeloid leukemia after chemotherapy and allogeneic stem cell transplantation
url http://dx.doi.org/10.1155/2012/146463
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