title: Microarray Gene Expression Analysis to Evaluate Cell Type Specific Expression of Targets Relevant for Immunotherapy of Hematological Malignancies.
abstract: Cellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T cells. However, dependent on the tissue distribution of the antigens that are targeted, anti-tumor responses can be accompanied by undesired side effects. Therefore, detailed tissue distribution analysis is essential to estimate potential efficacy and toxicity of candidate targets for immunotherapy of hematological malignancies. We performed microarray gene expression analysis of hematological malignancies of different origins, healthy hematopoietic cells and various non-hematopoietic cell types from organs that are often targeted in detrimental immune responses after allogeneic stem cell transplantation leading to graft-versus-host disease. Non-hematopoietic cells were also cultured in the presence of IFN-γ to analyze gene expression under inflammatory circumstances. Gene expression was investigated by Illumina HT12.0 microarrays and quality control analysis was performed to confirm the cell-type origin and exclude contamination of non-hematopoietic cell samples with peripheral blood cells. Microarray data were validated by quantitative RT-PCR showing strong correlations between both platforms. Detailed gene expression profiles were generated for various minor histocompatibility antigens and B-cell surface antigens to illustrate the value of the microarray dataset to estimate efficacy and toxicity of candidate targets for immunotherapy. In conclusion, our microarray database provides a relevant platform to analyze and select candidate antigens with hematopoietic (lineage)-restricted expression as potential targets for immunotherapy of hematological cancers.
authors.affiliation: Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: M J
authors.identifier: 0000-0002-5934-9990
authors.initials: MJ
authors.lastname: Pont
authors.affiliation: Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: M W
authors.initials: MW
authors.lastname: Honders
authors.affiliation: Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands.|Department of Internal Medicine 5, Hematology and Oncology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: A N
authors.initials: AN
authors.lastname: Kremer
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: van Kooten
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Out
authors.affiliation: Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: P S
authors.initials: PS
authors.lastname: Hiemstra
authors.affiliation: Department of Nephrology and the Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: H C
authors.initials: HC
authors.lastname: de Boer
authors.affiliation: Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Jager
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: E
authors.initials: E
authors.lastname: Schmelzer
authors.affiliation: Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: R G
authors.initials: RG
authors.lastname: Vries
authors.affiliation: Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, the Netherlands.
authors.forename: A S
authors.initials: AS
authors.lastname: Al Hinai
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: W G
authors.initials: WG
authors.lastname: Kroes
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Monajemi
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.|Radboud Institute for Molecular Life Science, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Goeman
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Böhringer
authors.affiliation: Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: W A F
authors.initials: WA
authors.lastname: Marijt
authors.affiliation: Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: J H F
authors.initials: JH
authors.lastname: Falkenburg
authors.affiliation: Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Griffioen
mesh_terms: D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007167:Immunotherapy; D007249:Inflammation / Q000473:pathology; D007371:Interferon-gamma / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D012044:Regression Analysis; D015203:Reproducibility of Results; D012867:Skin / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D007371:Interferon-gamma