WT1, PRAME, and PR3 mRNA Expression in Acute Myeloid Leukemia (AML)
| Autor: | Helga Schmetzer, Hans-Jochem Kolb, Daniel Christoph Amberger, Johanna Tischer, Tanja Kroell, Brigitte Steger, Lajos Floro |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Cancer Research Myeloid medicine.medical_treatment Immunology Gene Expression 03 medical and health sciences 0302 clinical medicine Antigen Antigens Neoplasm Cell Line Tumor Biomarkers Tumor Humans Immunology and Allergy Medicine RNA Messenger WT1 Proteins Neoplasm Staging Retrospective Studies Pharmacology PRAME Gene Expression Regulation Leukemic business.industry Melanoma Disease Management Myeloid leukemia Immunotherapy Prognosis medicine.disease Leukemia Myeloid Acute 030104 developmental biology Real-time polymerase chain reaction medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Female Bone marrow business Peptide Hydrolases |
| Zdroj: | Journal of Immunotherapy. 43:204-215 |
| ISSN: | 1524-9557 |
| DOI: | 10.1097/cji.0000000000000322 |
| Popis: | Several tumor-associated antigens (TAAs) were recently identified, that could qualify as targets for immunotherapy, they could qualify (on RNA-level) for monitoring of tumor load. Here, we studied the expression levels of the immunogenic antigens PRAME (preferentially expressed antigen of melanoma), WT1 (Wilms' tumor gene), and PR3 (proteinase 3) on myeloid blasts by real-time quantitative polymerase chain reaction and correlated these data to the state and course of disease and to the defined subgroups of acute myeloid leukemia (AML). At first diagnoses, 41 of 47 patients tested showed overexpression of PRAME (87%), 38 of WT1 (81%), and 26 of PR3 (55%), with the highest expression levels for PRAME (2048-fold), followed by WT1 (486-fold) and PR3 (196-fold). Thereby, with 70%, the most frequent combination at first diagnoses was detected to be PRAME and WT1 (33/47 patients). Overall, 21 patients (45%) revealed overexpression for all 3 TAAs. Moreover, the highest expression levels of PRAME were found to be correlated with the FAB subtype M5, cytogenetic unfavorable risk groups, and AMLs arising from myelodysplasia (secondary AML; P=0.02). To compare TAA expression levels in the course of disease, expression data were calculatory adjusted to 100% blasts, revealing a relative increase in the PRAME expression levels during the course of persistent disease (3/4 cases). Independent of stage of disease, by trend, higher TAA expression levels were found on blasts derived from peripheral blood than those derived from the bone marrow. In conclusion, it is suggested that vaccine strategies for cancer immunotherapy should comprise different TAA peptides anticipating the diverse TAA expression levels on blasts evolving during the course of disease or treatment. |
| Databáze: | OpenAIRE |
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