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Steger, B. ; Floro, L. ; Amberger, D.C.* ; Kroell, T.* ; Tischer, J.* ; Kolb, H.J. ; Schmetzer, H.

WT1, PRAME, and PR3 mRNA expression in acute myeloid leukemia (AML).

J. Immunother. 43, 204-215 (2020)
Postprint DOI PMC
Open Access Green
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Acute Myeloid Leukemia ; Dendritic Cells ; Tumor-associated Antigens (taa) ; Leukemia-associated Antigens (laa) ; Wt1 ; Prame ; Pr3 ; T Lymphocytes ; Immunotherapy ; Monitoring; Minimal Residual Disease; Rhamm-r3 Peptide Vaccination; Stem-cell Transplantation; Cytotoxic T-lymphocytes; Time Quantitative Pcr; Gene-expression; Myelodysplastic Syndrome; Myelogenous Leukemia; Clinical Importance; Proteinase-3
ISSN (print) / ISBN 1524-9557
e-ISSN 1537-4513
Zeitschrift Journal of Immunotherapy
Quellenangaben Band: 43, Heft: 6, Seiten: 204-215 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Verlagsort Two Commerce Sq, 2001 Market St, Philadelphia, Pa 19103 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CCG Immunotherapy (KKG-KIT)