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2 results on '"Joseph Kauer"'

1. Expression of the immune checkpoint modulator OX40 indicates poor survival in acute myeloid leukemia

Author

Maddalena Marconato, Joseph Kauer, Helmut R. Salih, Melanie Märklin, and Jonas S. Heitmann

Subjects
Medicine, Science
Abstract

Abstract Despite therapeutic advances, mortality of Acute Myeloid Leukemia (AML) is still high. Currently, the determination of prognosis which guides treatment decisions mainly relies on genetic markers. Besides molecular mechanisms, the ability of malignant cells to evade immune surveillance influences the disease outcome and, among others, the expression of checkpoints modulators contributes to this. In AML, functional expression of the checkpoint molecule OX40 was reported, but the prognostic relevance of OX40 and its ligand OX40L axis has so far not been investigated. Here we described expression and prognostic relevance of the checkpoint modulators OX40 and OX40L, analyzed on primary AML cells obtained from 92 therapy naïve patients. Substantial expression of OX40 and OX40L on AML blasts was detected in 29% and 32% of the investigated subjects, respectively, without correlation between the expression of the receptor and its ligand. Whereas OX40L expression was not associated with different survival, patients with high expression levels of the receptor (OX40high) on AML blasts survived significantly shorter than OX40low patients (p = 0.009, HR 0.46, 95% CI 0.24–0.86), which identifies OX40 as novel prognostic marker and a potential therapeutic target in AML patients.

Published
2022
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2. CD105 (Endoglin) as negative prognostic factor in AML

Author

Joseph, Kauer, Karolin, Schwartz, Claudia, Tandler, Clemens, Hinterleitner, Malte, Roerden, Gundram, Jung, Helmut R, Salih, Jonas S, Heitmann, and Melanie, Märklin

Subjects
Adult, Aged, 80 and over, Male, Neovascularization, Pathologic, Gene Expression Regulation, Leukemic, Immunology, lcsh:R, Endoglin, Endothelial Cells, lcsh:Medicine, Middle Aged, Prognosis, Disease-Free Survival, Article, Acute myeloid leukaemia, Leukemia, Myeloid, Acute, hemic and lymphatic diseases, Biomarkers, Tumor, Humans, Female, lcsh:Q, lcsh:Science, Aged
Abstract

While several genetic and morphological markers are established and serve to guide therapy of acute myeloid leukaemia (AML), there is still profound need to identify additional markers to better stratify patients. CD105 (Endoglin) is a type I transmembrane protein reported to induce activation and proliferation of endothelial cells. In addition, CD105 is expressed in haematological malignancies and the vessels of solid tumours. Here, CD105 associates with unfavourable disease course, but so far no data are available on the prognostic relevance of CD105 in haematological malignancies. We here generated a novel CD105 antibody for analysis of expression and prognostic relevance of CD105 in a cohort of 62 AML patients. Flow cytometric analysis revealed substantial expression in the various AML FAB types, with FAB M3 type displaying significantly lower surface levels. Next we established a cut-off specific fluorescence level of 5.22 using receiver-operating characteristics, which allowed to group patients in cases with CD105lo and CD105hi surface expression and revealed that high CD105 expression correlated significantly with poor overall and progression free survival. In conclusion, we here identify CD105 expression as a novel prognostic marker in AML, which may serve to optimize follow up and treatment decisions for AML patients.

Published
2019

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