Titel Deelnemers "Korte inhoud" "Deciphering the Non-Coding RNA Landscape of Pediatric Acute Myeloid Leukemia" "Jolien Vanhooren, Laurens Van Camp, Barbara Depreter, V. Martijn De Jong, Anne Uyttebroeck, An Van Damme, Laurence Dedeken, Jutte Van Der Werff Ten Bosch, Mattias Hofmans, Jan Philippé, Barbara De Moerloose, Tim Lammens" "Pediatric acute myeloid leukemia (pedAML) is a heterogeneous blood cancer that affects children. Although survival rates have significantly improved over the past few decades, 20-30% of children will succumb due to treatment-related toxicity or relapse. The molecular characterization of the leukemic stem cell, shown to be responsible for relapse, is needed to improve treatment options and survival. Recently, it has become clear that non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play a role in the development of human diseases, including pediatric cancer. Nevertheless, non-coding RNA expression data in pedAML are scarce. Here, we explored lncRNA (n = 30,168) and miRNA (n = 627) expression in pedAML subpopulations (leukemic stem cells (LSCs) and leukemic blasts (L-blasts)) and their normal counterparts (hematopoietic stem cells and control myeloblasts). The potential regulatory activity of differentially expressed lncRNAs in LSCs (unique or shared with the L-blast comparison) on miRNAs was assessed. Moreover, pre-ranked gene set enrichment analyses of (anti-) correlated protein-coding genes were performed to predict the functional relevance of the differentially upregulated lncRNAs in LSCs (unique or shared with the L-blast comparison). In conclusion, this study provides a catalog of non-coding RNAs with a potential role in the pathogenesis of pedAML, paving the way for further translational research studies." "The role of TARP as an antigen in cancer immunotherapy." "Jolien Vanhooren, Charlotte Derpoorter, Barbara Depreter, larissa deneweth, J. Philippe, Barbara De Moerloose, Tim Lammens" "In recent decades, immunotherapy has become a pivotal element in cancer treatment. A remaining challenge is the identification of cancer-associated antigens suitable as targets for immunotherapeutics with potent on-target and few off-tumor effects. The T-cell receptor gamma (TCRγ) chain alternate reading frame protein (TARP) was first discovered in the human prostate and androgen-sensitive prostate cancer. Thereafter, TARP was also identified in breast and endometrial cancers, salivary gland tumors, and pediatric and adult acute myeloid leukemia. Interestingly, TARP promotes tumor cell proliferation and migration, which is reflected in an association with worse survival. TARP expression in malignant cells, its role in oncogenesis, and its limited expression in normal tissues raised interest in its potential utility as a therapeutic target, and led to development of immunotherapeutic targeting strategies. In this review, we provide an overview of TARP expression, its role in different cancer types, and currently investigated TARP-directed immunotherapeutic options." "Long Non-Coding RNAs as Novel Therapeutic Targets in Juvenile Myelomonocytic Leukemia. I" "Mattias Hofmans, Tim Lammens, Barbara Depreter" "Juvenile myelomonocytic leukemia (JMML) treatment primarily relies on hematopoietic stem cell transplantation and results in long-term overall survival of 50–60%, demonstrating a need to develop novel treatments. Dysregulation of the non-coding RNA transcriptome has been demonstrated before in this rare and unique disorder of early childhood. In this study, we investigated the therapeutic potential of targeting overexpressed long non-coding RNAs (lncRNAs) in JMML. Total RNA sequencing of bone marrow and peripheral blood mononuclear cell preparations from 19 untreated JMML patients and three healthy children revealed 185 differentially expressed lncRNA genes (131 up- and 54 downregulated). LNA GapmeRs were designed for 10 overexpressed and validated lncRNAs. Molecular knockdown (≥ 70% compared to mock control) after 24 h of incubation was observed with two or more independent GapmeRs in 6 of them. For three lncRNAs (lnc-THADA-4, lnc-ACOT9-1 and NRIR) knockdown resulted in a significant decrease of cell viability after 72 h of incubation in primary cultures of JMML mononuclear cells, respectively. Importantly, the extent of cellular damage correlated with the expression level of the lncRNA of interest. In conclusion, we demonstrated in primary JMML cell cultures that knockdown of overexpressed lncRNAs such as lnc-THADA-4, lnc-ACOT9-1 and NRIR may be a feasible therapeutic strategy." "Routine haematology parameters in COVID-19 patients and clinical outcome" "Simke Demeester, Thomas Demuyser, Charlotte Fauconnier, Robbe Heestermans, Christelle Orlando, Barbara Depreter, Kristin Jochmans"