Impaired immunity against infection and cancer
The prize for the best experimental paper goes to our Scientific Director and Principal Investigator at St. Anna CCRI, Prof. Kaan Boztug, MD, senior author of the publication Germline biallelic mutation affecting the transcription factor Helios causes pleiotropic defects of immunity (Shahin et al. Science Immunology 2021). Kaan Boztug and colleagues identified a previously unknown defect in hematopoiesis and immunity. This defect arises due to a biallelic gene defect (i.e. a defect in both copies of a particular gene) in Helios, a transcription factor named after the Greek sun god, i.e. a protein responsible for regulating gene expression. While somatic mutations in Helios, i.e. mutations acquired during life, are common in some leukemias, the researchers now for the first time identified a disease with a congenital defect and elucidated new functions of Helios.
In the paper Identification of germline monoallelic mutations in IKZF2 in patients with immune dysregulation by Daniel Mayr, MD student in the Boztug research group, which was selected as Best Abstract at the conference, the sun god Helios is once again at the center of immunodeficiency research. Mayr et al. were able to show that mutant monoallelic Helios variants exhibited a disrupted network of interaction partners. “This newly discovered germline mutation in Helios disrupts its interaction with other proteins. This, in turn, negatively affects immunity, so that the immune response against infections and precancerous cells is impaired. These findings support future efforts to develop targeted treatments for immunodeficiency and malignant tumors,” explains Kaan Boztug.
In the same context, the presentation Monoallelic and Biallelic Germline Mutations Affecting the Transcription Factor Helios cause Pleiotropic Defects of Immunity by Daniel Mayr, was selected as the “Best Abstract” of the meeting. Mayr is co-first author of the corresponding publication and research assistant in the Boztug research group (see below).
Go to publications:
Irradiation increases survival rate in high-risk leukemia
Prof. Christina Peters, MD, affiliated clinician at St. Anna CCRI and senior physician at St. Anna Children’s Hospital, receives the award for the best clinical paper, honoring her publication Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study (Peters et al. Journal of Clinical Oncology 2021). Acute lymphoblastic leukemia (ALL) is the most common cancer in children, generally curable with contemporary chemotherapy. However, if the disease is classified as high-risk ALL and a stem cell transplantation becomes inevitable, total body irradiation is still the treatment of choice prior to transplantation. This was the conclusion drawn from the FORUM study, including 35 countries on five continents.
“As the largest study on this topic to date, we published the results in the top-ranked Journal of Clinical Oncology. Soon after that, the journal Frontiers invited us – the international transplant consortium for ALL – to publish a collection of reviews and scientific reports on ALL in children,” reports Peters, who serves as co-editor of the resulting “Research Topic” in Frontiers. Although total body irradiation and stem cell transplantation can be life-saving in high-risk ALL, long-term side effects sometimes have a massive impact on the quality of life of children and young adults. Hence, there was a dire need to clearly outline recent and previously published data, as well as to discuss potential new approaches, as did the aforementioned research topic.
Go to publication: https://ascopubs.org/doi/full/10.1200/JCO.20.02529
Frontiers Research Topic: https://www.frontiersin.org/research-topics/19704/allogeneic-hematopoetic-stem-cell-transplantation-for-children-with-acute-lymphoblastic-leukemia-in#overview
Gene defect shortens survival and needs targeted treatment
The prize for the best oncological paper is awarded to Ulrike Pötschger, PhD, Head of Statistics in Ruth Ladenstein’s group “Studies & Statistics for Integrated Research and Projects” (S2IRP) for the publication Frequency and Prognostic Impact of ALK Amplifications and Mutations in the European Neuroblastoma Study Group (SIOPEN) High-Risk Neuroblastoma Trial (HR-NBL1; Bellini, Poetschger, et al. Journal of Clinical Oncology 2021). The study revealed that neuroblastomas, the most common solid tumors outside the brain in children, are associated with poorer survival when they harbor genetic alterations in the ALK gene and belong to the high-risk group.
“The anaplastic lymphoma kinase ALK is a protein that, if activated, fuels tumor growth. “Our data form the basis of an upcoming pan-European therapeutic trial evaluating the use of an ALK inhibitor together with chemotherapy and immunotherapy at the beginning of the treatment of high-risk neuroblastoma with alterations in the ALK gene. Our goal is to significantly improve the prognosis of these patients through this targeted therapy,” emphasizes co-first author Ulrike Pötschger.
Go to publication: https://ascopubs.org/doi/full/10.1200/JCO.21.00086
We congratulate all award winners!
About Kaan Boztug
Univ.-Prof. Dr. med. Kaan Boztug, born in Eregli/Turkey, studied Medicine in Düsseldorf, Freiburg and London. In 2011, he joined the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences in Vienna as Principal Investigator, establishing his own research group. He is a physician and Professor of Pediatrics and Inflammation Research at the Department of Pediatrics and Adolescent Medicine at the Medical University Vienna. He is a Consultant in Pediatric Hematology/Oncology & Head of Pediatric Immunology at the St. Anna Children’s Hospital, has headed the Vienna Center for Rare and Undiagnosed Diseases (CeRUD) since 2014, and has been the Director of the Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases since 2016. Since March 2019, he heads the St. Anna Children’s Cancer Research Institute as Scientific Director.
About Daniel Mayr
Daniel Mayr is in his 6th year of medical studies at the Medical University of Vienna with excellent success (merit scholarship). Since 2018, he also works as a research assistant in Kaan Boztug´s group “Immunodeficiency, Cancer Predisposition & Precision Oncology” at St. Anna Children´s Cancer Research Institute (St. Anna CCRI). His research experience includes state of the art wet-lab techniques to dissect the pathomechanism of two novel inborn errors of immunity caused by mutations in SYK and HELIOS. He also coordinated and authored the largest global clinical study on the clinical phenotype, immunophenotype and stem cell transplantation in IL21R deficient patients. Before that, he established an automated microscopy platform for high throughput live imaging of zebrafish xenografts in Martin Distel´s “Innovative Cancer Models” group at St. Anna CCRI. Currently, he is completing his clinical clerkship at the Hematology and Oncology Department at St. Anna Children’s Hospital.
About Christina Peters
Christina Peters, MD, is Professor of Pediatrics at the Department of Stem Cell Transplantation of St. Anna Children’s Hospital and Affiliated Clinician at St. Anna Children’s Cancer Research Institute in Vienna. She is principal investigator of active studies within the European Society for Blood and Marrow Transplantation (EBMT) and the International Berlin Frankfurt Münster Study Group (IBFM) for the treatment of pediatric leukemia. Her research interests include allogeneic hematopoietic transplantation in children and adolescents with malignant and non-malignant diseases from related and unrelated donors, infectious and toxic complications after stem cell transplantation, adoptive therapies for hematological malignancies and family oriented rehabilitation for children with life threatening diseases. Christina Peters chaired the EBMT Pediatric Diseases Working Party between 2008 and 2014. She has authored and co-authored numerous papers in peer-review journals such as The Lancet, The New England Journal of Medicine, orThe Journal of Clinical Oncology. Christina Peters acts as a regular reviewer of publications for hematology, pediatric and leukemia journals. She is a member of many professional societies including IBFM, the Center for International Blood and Marrow Transplant Research (CIBMTR), the German and Austrian Society of Pediatric Hematology and the Austrian Gene Therapy Commission. Furthermore, Christina Peters is a member of the Advisory Board of the Austrian Ministry of Health, the Bioethical committee of the Austrian Prime Minister and member of the European Network Pediatric Research at the European Medicines Agency EMA (ENPREMA).
About Ulrike Pötschger
Ulrike graduated in Statistics at the University of Vienna and obtained a PhD at the Medical University of Vienna. Ulrike is the leader of the statistical team of the S²IRP/CCRI and is lead study statistician or as member of the DMC of many international trials in paediatric oncology. Ulrike is the chair of the Information Management and Methodology committee of the I-BFM and the chair of the statistical committee of SIOP-EN and was statistician of the paediatric working party of the EBMT. Ulrike authored and co-authored more than 120 research papers and since 2011, Ulrike is an external lecturer at the Medical University of Vienna. Her main methodological interest is on the pseudo-value regression, a novel statistical model that allows to study the impact of predictors on long-term survival probabilities.