Review
Oncology
Claudia Finana, Noel Gomez-Molina, Sandra Alonso-Moreno, Laura Belver
Summary: Juvenile myelomonocytic leukemia (JMML) is a rare childhood blood cancer characterized by RAS signaling hyperactivation and genetic and epigenetic alterations. The recent international consensus on JMML stratification has classified the disease into three clinical groups based on DNA methylation status. However, our understanding of JMML origin, cell identity, and heterogeneity remains limited.
Article
Hematology
Hironobu Kitazawa, Yusuke Okuno, Hideki Muramatsu, Kosuke Aoki, Norihiro Murakami, Manabu Wakamatsu, Kyogo Suzuki, Kotaro Narita, Shinsuke Kataoka, Daisuke Ichikawa, Motoharu Hamada, Rieko Taniguchi, Nozomu Kawashima, Eri Nishikawa, Atsushi Narita, Nobuhiro Nishio, Asahito Hama, Mignon L. Loh, Elliot Stieglitz, Seiji Kojima, Yoshiyuki Takahashi
Summary: JMML patients were classified into high and low methylation groups using Digital Restriction Enzyme Analysis of Methylation (DREAM), and further divided into different risk groups by a support vector machine (SVM). Patients with HM_SVM profile had significantly poorer 5-year overall survival rate compared to those with LM_SVM profile.
Article
Oncology
Xuewei Hao, Jun Zhang, Guoyou Chen, Weiwei Cao, Hongyang Chen, Shuo Chen
Summary: This study demonstrates that low expression of GSTM5 and its high DNA methylation status may serve as a novel potential molecular target gene for lung adenocarcinoma (LUAD).
Article
Immunology
Eleni Louka, Benjamin Povinelli, Alba Rodriguez-Meira, Gemma Buck, Wei Xiong, Guanlin Wang, Nikolaos Sousos, Neil Ashley, Angela Hamblin, Christopher A. G. Booth, Anindita Roy, Natalina Elliott, Deena Iskander, Josu de la Fuente, Nicholas Fordham, Sorcha O'Byrne, Sarah Inglott, Ruggiero Norfo, Mariolina Salio, Supat Thongjuea, Anupama Rao, Irene Roberts, Adam J. Mead
Summary: Juvenile myelomonocytic leukemia (JMML) is a childhood leukemia with poor prognosis caused by RAS-pathway mutations. The cellular hierarchy of JMML is complex, with LSCs present in HSPCs, providing new avenues for monitoring and treating the disease.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Cell Biology
Anna Dal Molin, Mattias Hofmans, Enrico Gaffo, Alessia Buratin, Helene Cave, Christian Flotho, Valerie de Haas, Charlotte M. Niemeyer, Jan Stary, Pieter Van Vlierberghe, Jan Philippe, Barbara De Moerloose, Geertruij te Kronnie, Silvia Bresolin, Tim Lammens, Stefania Bortoluzzi
Summary: JMML is characterized by clonal growth of RAS signaling addicted stem cells, with specific mutations defining subtypes and distinct gene, miRNA, and long non-coding RNA expression profiles. This study focused on circRNAs, identifying dysregulated circRNAs and showing expression differences among molecular subgroups of JMML. Validation in an independent cohort confirmed up-regulation of circMCTP1 and its connection to tumor suppressor miRNAs, linking dysregulated circRNAs to regulatory networks.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Hematology
Charlotte M. Niemeyer, Christian Flotho, Daniel B. Lipka, Jan Stary, Claudia Rossig, Andre Baruchel, Thomas Klingebiel, Concetta Micalizzi, Gerard Michel, Karsten Nysom, Susana Rives, Markus Schmugge Liner, Marco Zecca, Maximilian Schoenung, Irith Baumann, Peter Nollke, Bouchra Benettaib, Noha Biserna, Jennifer Poon, Mathew Simcock, Meera Patturajan, Daniel Menezes, Allison Gaudy, Marry M. Van den Heuvel-Eibrink, Franco Locatelli
Summary: Azacitidine monotherapy is a feasible option for children with newly diagnosed JMML, providing valuable clinical benefits prior to HSCT. Long-term safety and efficacy data in this population are still needed for full elucidation.
Review
Medicine, General & Internal
Christina Mayerhofer, Charlotte M. Niemeyer, Christian Flotho
Summary: JMML is a rare pediatric leukemia characterized by mutations in RAS pathway genes, with treatment options based on genetic profile and disease severity. Management can include medication or allogeneic hematopoietic stem cell transplantation tailored to individual patient needs.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Oncology
Maximilian Schoenung, Julia Meyer, Peter Noellke, Adam B. Olshen, Mark Hartmann, Norihiro Murakami, Manabu Wakamatsu, Yusuke Okuno, Christoph Plass, Mignon L. Loh, Charlotte M. Niemeyer, Hideki Muramatsu, Christian Flotho, Elliot Stieglitz, Daniel B. Lipka
Summary: DNA methylation patterns in JMML can serve as a biomarker for patient stratification. This study established three DNA methylation subgroups and developed a classifier with 98% accuracy, which can classify patients across different technological platforms to guide clinical treatment decisions.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Ying Wu, Patricia M. A. Zehnle, Jovana Rajak, Naile Koleci, Geoffroy Andrieux, Lorena Gallego-Villar, Konrad Aumann, Melanie Boerries, Charlotte M. Niemeyer, Christian Flotho, Sheila Bohler, Miriam Erlacher
Summary: JMML cells rely on both MCL-1 and BCL-XL for survival, and azacitidine and BH3 mimetic drugs can effectively target these proteins. Azacitidine acts in vivo through downregulation of MCL-1 and upregulation of BH3-only. Combination treatment of azacitidine with BCL-XL inhibition is more effective in eliminating JMML cells compared to BCL-2 inhibition. These findings highlight the need for clinically applicable MCL-1 or BCL-XL inhibitors in JMML refractory to standard therapy.
Article
Gastroenterology & Hepatology
Kalliopi Zachou, Pinelopi Arvaniti, Aggeliki Lyberopoulou, Eirini Sevdali, Matthaios Speletas, Maria Ioannou, George K. Koukoulis, Yves Renaudineau, George N. Dalekos
Summary: This study investigated the alterations of DNA methylation in peripheral lymphocytes of patients with autoimmune hepatitis (AIH) at diagnosis and remission. The results showed abnormal expressions of TET1 and DNMT3A in AIH patients' lymphocytes, which were associated with disease activity and may affect immunological pathways.
LIVER INTERNATIONAL
(2022)
Article
Biochemistry & Molecular Biology
Ying Gan, Congcong Cao, Aolin Li, Haifeng Song, Guanyu Kuang, Binglei Ma, Quan Zhang, Qian Zhang
Summary: TRIM58 is frequently downregulated in ccRCC tissues due to promoter methylation, associated with tumor nuclear grade and poor patient survival. TRIM58-TET1 can directly induce TRIM58 CpG island demethylation, activate TRIM58 transcription, and significantly inhibit cell proliferation and migration.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Review
Pharmacology & Pharmacy
Yao Dai, Danian Chen, Tingting Xu
Summary: Atherosclerosis is a pathological process involving lipid oxidation, immune system activation, and endothelial dysfunction. DNA methylation, as one of the most important epigenetic mechanisms, plays a key role in the pathogenesis of atherosclerosis. This review discusses the abnormal changes of DNA methylation in atherosclerosis, including genome-wide hypermethylation with aging, hypermethylation linked to methyl supply and hyperhomocysteinemia, and the influence of oxidative stress on demethylation processes. The review also summarizes the current status of epigenetic treatment for atherosclerosis, providing new directions and potential therapeutic targets.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Ryszard Olinski, Geir Slupphaug, Marek Foksinski, Hans Einar Krokan
Summary: The DNA of living cells undergoes continuous structural and chemical changes due to fundamental cellular metabolic processes and reactions with normal cellular metabolites. These modifications include enzymatically oxidized bases, aberrantly methylated bases, deaminated bases, and uracil generated from deaminated cytosine. These alterations can impact base-pairing properties, leading to replicative and transcriptional mutagenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Mattias Hofmans, Tim Lammens, Barbara Depreter, Ying Wu, Miriam Erlacher, Aurelie Caye, Helene Cav, Christian Flotho, Valerie de Haas, Charlotte M. Niemeyer, Jan Stary, Filip Van Nieuwerburgh, Dieter Deforce, Wouter Van Loocke, Pieter Van Vlierberghe, Jan Philipp, Barbara De Moerloose
Summary: In this study, targeting overexpressed long non-coding RNAs (lncRNAs) in JMML was investigated as a therapeutic strategy. Knockdown of three lncRNAs (lnc-THADA-4, lnc-ACOT9-1, and NRIR) resulted in a significant decrease in cell viability in primary JMML cell cultures, with cellular damage correlating with the expression level of the lncRNA of interest. This study suggests that targeting overexpressed lncRNAs may be a viable therapeutic approach for JMML.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Natascia Marino, Rana German, Ram Podicheti, Douglas B. Rusch, Pam Rockey, Jie Huang, George E. Sandusky, Constance J. Temm, Sandra Althouse, Kenneth P. Nephew, Harikrishna Nakshatri, Jun Liu, Ashley Vode, Sha Cao, Anna Maria Storniolo
Summary: This study found molecular aberrations in normal breast tissue of women at high risk for breast cancer, which may contribute to breast cancer susceptibility. This is also the first study to molecularly characterize true normal breast tissue.
CLINICAL EPIGENETICS
(2022)
Article
Biochemical Research Methods
Phillip Loehr, Stefan Schiele, Tim Tobias Arndt, Stefanie Gruetzner, Rainer Claus, Christoph Roemmele, Gernot Mueller, Christoph Schmid, Kevin M. Dennehy, Andreas Rank
Summary: This study analyzed the changes in lymphocyte subsets in COVID-19 patients and found that cell counts of lymphocytes and their subsets are reduced in severe cases. Age and gender also play a role in the altered cell counts.
Review
Oncology
Serena Ilaria Tripodi, Elena Bergami, Arianna Panigari, Valentina Caissutti, Carlotta Brovia, Marica De Cicco, Emanuele Cereda, Riccardo Caccialanza, Marco Zecca
Summary: Nutrition plays an increasingly important role in the health and growth of children, especially those facing cancer. This article reviews nutritional assessment methods and interventions for children with cancer. The key findings highlight the importance of monitoring the nutritional status and body composition of oncologic children, as well as the need for skilled clinical nutrition personnel.
Article
Clinical Neurology
Anne Sophie L. Helligsoe, Louise T. Henriksen, Line Kenborg, Yasmin Lassen-Ramshad, Lisa M. Wu, Jeanette F. Winther, Henrik Hasle, Ali Amidi
Summary: This study examined neurocognitive function in childhood brain tumor survivors and its associations with quality of life (QoL) and symptom burden. The majority of survivors exhibited overall neurocognitive impairment, reduced QoL, and high symptom burden.
NEURO-ONCOLOGY PRACTICE
(2023)
Letter
Biophysics
Luca Vinci, Christian Flotho, Peter Noellke, Dirk Lebrecht, Riccardo Masetti, Valerie de Haas, Barbara De Moerloose, Michael Dworzak, Henrik Hasle, Tayfun Guengoer, Jan Stary, Dominik Turkiewicz, Marek Ussowicz, Cristina Diaz de Heredia, Jochen Buechner, Kirsi Jahnukainen, Krisztian Kallay, Ivana Bodova, Owen P. P. Smith, Marco Zecca, Dorine Bresters, Peter Lang, Tania Nicole Masmas, Roland Meisel, Herbert Pichler, Miriam Erlacher, Gudrun Goehring, Franco Locatelli, Brigitte Strahm, Charlotte M. M. Niemeyer, Ayami Yoshimi
BONE MARROW TRANSPLANTATION
(2023)
Article
Hematology
Sarah Weischendorff, Silvia De Pietri, Mathias Rathe, Thomas Leth Frandsen, Henrik Hasle, Claus H. Nielsen, Claus Moser, Klaus Mueller
Summary: This study investigated whether measurements of neutrophil chemotaxis could be used as risk markers for bloodstream infections (BSI) in children with acute lymphoblastic leukemia (ALL). The results showed that patients who developed BSI during induction treatment had increased levels of chemokines CXCL1 and CXCL8, suggesting that these markers may help identify patients at increased risk of BSI during chemotherapy-induced neutropenia.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2023)
Editorial Material
Radiology, Nuclear Medicine & Medical Imaging
Johanna S. S. Enke, Nic G. G. Reitsam, Tina Schaller, Rainer Claus, Constantin Lapa, Alexander Dierks
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Article
Medicine, General & Internal
Barbara Eichhorst, Carsten U. Niemann, Arnon P. Kater, Moritz Fuerstenau, Julia von Tresckow, Can Zhang, Sandra Robrecht, Michael Gregor, Gunnar Juliusson, Patrick Thornton, Philipp B. Staber, Tamar Tadmor, Vesa Lindstrom, Caspar da Cunha-Bang, Christof Schneider, Christian B. Poulsen, Thomas Illmer, Bjoern Schoettker, Thomas Noesslinger, Ann Janssens, Ilse Christiansen, Michael Baumann, Henrik Frederiksen, Marjolein van der Klift, Ulrich Jaeger, Maria B. L. Leys, Mels Hoogendoorn, Kourosh Lotfi, Holger Hebart, Tobias Gaska, Harry Koene, Lisbeth Enggaard, Jereon Goede, Josien C. Regelink, Anouk Widmer, Florian Simon, Nisha De Silva, Anna-Maria Fink, Jasmin Bahlo, Kirsten Fischer, Clemens-Martin Wendtner, Karl A. Kreuzer, Matthias Ritgen, Monika Brueggemann, Eugen Tausch, Mark-David Levin, Marinus van Oers, Christian Geisler, Stephan Stilgenbauer, Michael Hallek
Summary: In fit patients with CLL, venetoclax-obinutuzumab, with or without ibrutinib, showed superior results compared to chemoimmunotherapy as a first-line treatment, with higher rates of undetectable minimal residual disease and progression-free survival.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Oncology
Luise Victoria Claass, Patrick Mayr, Lisa Paschold, Thomas Weber, Denis Terziev, Bertram Jehs, Richard Brill, Johannes Dober, Bruno Maerkl, Claudia Wickenhauser, Piotr Czapiewski, Martin Trepel, Rainer Claus, Mascha Binder
Summary: SARS-CoV-2 vaccines do not seem to be associated with the development of lymphomas in the lymph nodes of the deltoid region used for vaccination. The study found that cases of unilateral axillary lymphomas occurred both before and after the introduction of SARS-CoV-2 vaccines, and there was no evidence of a correlation between the vaccines and the malignant clonotypes.
Article
Biophysics
Karl-Walter Sykora, Rita Beier, Ansgar Schulz, Simone Cesaro, Johann Greil, Jolanta Gozdzik, Petr Sedlacek, Peter Bader, Johannes Schulte, Marco Zecca, Franco Locatelli, Bernd Gruhn, Dirk Reinhardt, Jan Styczynski, Simona Piras, Franca Fagioli, Sonia Bonanomi, Maurizio Caniglia, Xieran Li, Joachim Baumgart, Jochen Kehne, Monika Mielcarek-Siedziuk, Krzysztof Kalwak
Summary: This study compared the safety and efficacy of busulfan and treosulfan in conditioning treatment for children with non-malignant diseases prior to hematopoietic stem cell transplantation. The results showed that treosulfan had a higher rate of treatment success and overall survival, but a higher rate of graft failure. Busulfan and treosulfan had similar adverse events.
BONE MARROW TRANSPLANTATION
(2023)
Article
Hematology
V. Munaretto, P. Corti, E. Bertoni, S. I. Tripodi, M. E. Guerzoni, S. Cesaro, F. Arcioni, C. Piccolo, T. Mina, M. Zecca, D. Cuzzubbo, M. Casale, G. Palazzi, L. D. Notarangelo, N. Masera, P. Samperi, S. Perrotta, G. Russo, L. Sainati, R. Colombatti
Summary: Acute chest syndrome (ACS) is a common reason for hospitalization in sickle cell disease (SCD). Despite advances in acute care, many settings lack knowledge about ACS best practices. A retrospective study in Italy showed that standardized management improved diagnostic and therapeutic pathways of ACS in children, but discrepancies were found between reference centers and general hospitals.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Medicine, Research & Experimental
Lisa Schweizer, Tina Schaller, Maximilian Zwiebel, Oezge Karayel, Johannes Bruno Mueller-Reif, Wen-Feng Zeng, Sebastian Dintner, Thierry M. Nordmann, Klaus Hirschbuehl, Bruno Maerkl, Rainer Claus, Matthias Mann
Summary: SARS-CoV-2 can cause damage to lung tissue and other organs in the human body, and this study aimed to analyze these effects comprehensively. Using a mass spectrometry proteomics workflow, the researchers identified inflammatory responses as the initial reaction in all tissues. They also found specific patterns of damage in different organs, such as diffuse alveolar damage in the lungs and organ-specific changes in the kidneys, liver, and lymphatic and vascular systems. In the brain, secondary inflammatory effects were linked to neurotransmitter receptors and myelin degradation. These findings contribute to our understanding of the mechanisms of COVID-19 and provide insights for organ-specific therapeutic interventions.
EMBO MOLECULAR MEDICINE
(2023)
Article
Oncology
Thomas N. N. Nissen, Catherine Rechnitzer, Birgitte K. K. Albertsen, Lotte Borgwardt, Vibeke B. B. Christensen, Eva Fallentin, Henrik Hasle, Lars S. S. Johansen, Lisa L. L. Maroun, Karin B. B. Nissen, Allan Rasmussen, Mathias Rathe, Steen Rosthoj, Nicolai A. A. Schultz, Peder S. S. Wehner, Marianne H. H. Jorgensen, Jesper Brok
Summary: This study reports the incidence, outcomes, and long-term adverse events of malignant liver tumors in Danish children over the past 35 years. The overall incidence of liver tumors in Danish children was approximately 2.29 per 1 million children per year, with hepatoblastoma being the most common tumor. The overall 5-year survival rate was 84% and 78% for hepatoblastomas and hepatocellular carcinomas, respectively, with age≥8 years being the most significant factor associated with a poorer prognosis. Adverse events included reduced renal and cardiac function, as well as impaired hearing function, affecting a significant number of patients.
Article
Biochemical Research Methods
Robert Hanes, Pilar Ayuda-Duran, Leiv Ronneberg, Sigve Nakken, Eivind Hovig, Manuela Zucknick, Jorrit M. Enserink
Summary: screenwerk is an open-source tool for designing and analyzing drug combination screens, offering modularity, flexibility, and customization. It can be coupled with other R packages to identify synergistic and antagonistic drug interactions in cell lines or patient samples. screenwerk provides a complete solution for setting up drug sensitivity screens, performing quality control, and analyzing, reporting, and visualizing the results.
Article
Pediatrics
Chiara Ionio, Francesca Bigoni, Maddalena Sacchi, Marco Zecca, Elena Bergami, Marta Landoni, Giulia Ciuffo, Anna Rovati, Damiano Rizzi
Summary: This study aimed to explore the psychological and post-traumatic consequences of oncological disease in adolescents and their impact on the family system. The findings revealed that adolescent cancer patients had lower levels of psychological well-being and showed a significant influence of the traumatic event on their identity and life perspectives. The study also highlighted a positive correlation between adolescents' psychological well-being and their relationship with parents.
Article
Biochemical Research Methods
Ping-Han Hsieh, Camila Miranda Lopes-Ramos, Manuela Zucknick, Geir Kjetil Sandve, Kimberly Glass, Marieke Lydia Kuijjer
Summary: Gene co-expression measurements are widely used in computational biology to identify coordinated expression patterns. However, certain normalization methods can introduce false-positive associations between genes, hindering downstream co-expression network analysis. In this study, a normalization method called SNAIL (Smooth-quantile Normalization Adaptation for the Inference of co-expression Links) is developed to avoid false-positive associations and retain associations to genes expressed in small subgroups of samples. This method has the potential to impact network modeling and association-based approaches in large-scale heterogeneous data.