Publications by authors named "Koen Debackere"
Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of hematological cancers arising from the malignant transformation of mature T cells. In a cohort of 28 PTCL cases, we identified recurrent overexpression of MYCN, a member of the MYC family of oncogenic transcription factors. Approximately half of all PTCL cases was characterized by a MYC expression signature.
View Article and Find Full Text PDFArticle Synopsis
- Development of primary mediastinal B-cell lymphoma (PMBL) is influenced by unique genomic changes, particularly copy-neutral loss of heterozygosity (CN-LOH), setting it apart from other B-cell cancers.
- A study found that 91% of PMBL cases exhibited extensive CN-LOH regions, affecting multiple chromosomes, with the largest segments contributing to an average 9.9% loss of genetic diversity.
- The findings reveal that CN-LOH may play a significant role in the progression of PMBL, potentially serving as a second mutational hit that affects crucial driver genes like MHC I and B2M.
Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas with poor prognosis. Up to 30% of PTCL lack distinctive features and are classified as PTCL, not otherwise specified (PTCL-NOS). To further improve our understanding of the genetic landscape and biology of PTCL-NOS, we perform RNA-sequencing of 18 cases and validate results in an independent cohort of 37 PTCL cases.
View Article and Find Full Text PDFCorrection to: In-depth characterization of the tumor microenvironment in central nervous system lymphoma reveals implications for immune-checkpoint therapy.
Cancer Immunol Immunother
April 2021
Article Synopsis
- Primary central nervous system lymphoma (PCNSL) is a rare and serious type of cancer affecting the brain and spinal cord.
- Researchers studied the tumor environment in PCNSL patients to see how cells that fight cancer, like T cells, were influenced by different factors like medications and virus presence.
- They found that the mix of immune cells in the tumor could help predict patient outcomes and suggest ways to improve treatments using immune-checkpoint therapies.
Glutamine metabolism provides synergistic support for macrophage activation and elicitation of desirable immune responses; however, the underlying mechanisms regulated by glutamine metabolism to orchestrate macrophage activation remain unclear. Here we show that the production of α-ketoglutarate (αKG) via glutaminolysis is important for alternative (M2) activation of macrophages, including engagement of fatty acid oxidation (FAO) and Jmjd3-dependent epigenetic reprogramming of M2 genes. This M2-promoting mechanism is further modulated by a high αKG/succinate ratio, whereas a low ratio strengthens the proinflammatory phenotype in classically activated (M1) macrophages.
View Article and Find Full Text PDFThe success of chemotherapy in cancer treatment is limited by scarce drug delivery to the tumor and severe side-toxicity. Prolyl hydroxylase domain protein 2 (PHD2) is an oxygen/redox-sensitive enzyme that induces cellular adaptations to stress conditions. Reduced activity of PHD2 in endothelial cells normalizes tumor vessels and enhances perfusion.
View Article and Find Full Text PDFA key function of blood vessels, to supply oxygen, is impaired in tumors because of abnormalities in their endothelial lining. PHD proteins serve as oxygen sensors and may regulate oxygen delivery. We therefore studied the role of endothelial PHD2 in vessel shaping by implanting tumors in PHD2(+/-) mice.
View Article and Find Full Text PDF