Important genetic predispositions for acute myeloid leukemia discovered

Common genetic factors increase the risk of developing acute myeloid leukemia (AML) during one’s lifetime. In the largest study ever performed in AML, an international team of researchers examined the genomes of more than 4,000 AML patients and around 10,500 healthy individuals. The study was led by researchers from Newcastle University, the Icahn School of Medicine at Mount Sinai (ISMMS, New York), the University Hospital Carl Gustav Carus Dresden, and the National Center for Tumor Diseases Dresden (NCT/UCC). The results provide the basis for exploring biological mechanisms that are key to the disease, and possibly developing preventive and improved therapeutic strategies in the future. The study was published in the renowned journal Nature Communications (https://doi.org/10.1038/s41467-021-26551-x).

The National Center for Tumor Diseases Dresden (NCT/UCC) is a joint institution of the German Cancer Research Center (DKFZ), the University Hospital Carl Gustav Carus Dresden, Carl Gustav Carus Faculty of Medicine at TU Dresden and the Helmholtz-Zentrum Dresden-Rossendorf (HZDR).

Acute myeloid leukemia (AML) is the most common form of rapidly progressive blood cancer in adults. It is fatal within a short time if left untreated. In most cases, the cause for the occurrence of the disease have been unclear. A large-scale international study led by researchers from Newcastle University, the Icahn School of Medicine at Mount Sinai (ISMMS, New York), the University Hospital Carl Gustav Carus Dresden and the National Center for Tumor Diseases Dresden (NCT/UCC) has now shown for the first time that common inherited genetic factors increase the risk of developing AML. Until now, this kind of association was known only for very rare genetic alterations in a few AML patients and their families. "The results provide an important basis for a deeper understanding of the disease and the biological mechanisms behind it. In the future, this could open up new possibilities for preventing and better treating the disease," says Professor James M. Allan of Newcastle University. "These results are the outcome of a joint effort and were only possible thanks to many years of successful collaboration between researchers and medical professionals from ten different countries."

As part of the genome-wide association study, researchers specifically examined those sites in the approximately three billion nucleotides of the normal human DNA sequence where the genetic material differs in a single nucleotide base ("letter") in at least one percent of the population. They investigated more than 7 million of these single nucleotide polymorphisms (SNPs) and detected an alteration in the KMT5B gene that was significantly more common in the more than 4,000 AML patients analyzed than in the comparison group of approximately 10,500 healthy individuals. The researchers also identified another genetic alteration in the HLA-DQB1 gene on chromosome 6p that was substantially more frequent in patients with normal karyotype AML, the most common subtype of this disease.

"We already know that one of the discovered risk genes plays an essential role in ensuring our immune system works properly. Consequently, our results show that a strong immune system protects us from developing AML, while a less efficient immune system increases the risk of developing AML," explains Professor Friedrich Stölzel from the University Hospital Dresden.

"The very clear correlation of genetic factors and the occurrence of AML suggests that inherited genetic variants are a key factor in the development of disease," said Professor Kenan Onel of the Icahn School of Medicine at Mount Sinai. “The relevant genetic traits are inherited and can be passed on within a family.”
Future studies will now investigate which biological mechanisms are triggered by the genetic changes in the body and how they contribute to the development of leukemia. On this basis, new strategies for the prevention and treatment of leukemia may be developed in the future.

Publication:
Lin, WY., Fordham, S.E., Hungate, E. et al. Genome-wide association study identifies susceptibility loci for acute myeloid leukemia. Nat Commun 12, 6233 (2021). https://doi.org/10.1038/s41467-021-26551-x

Contact:
Prof. Dr. Friedrich Stölzel
Carl Gustav Carus University Hospital, Medizinische Klinik I
Tel: + 49 351 458-5603
friedrich.stoelzel@uniklinikum-dresden.de

James M. Allan
Professor of Cancer Genetics, Translational and Clinical Research Institute,
Faculty of Medical Sciences, Newcastle University
Tel: +44 191 208 4435
james.allan@newcastle.ac.uk

A printable resolution image is available for the message:
https://www.nct-dresden.de/fileadmin/media/nct-dresden/das-nct/newsroom/pressemitteilungen/DNA-Aufbereitung.jpg
Caption: DNA from patients with acute myeloid leukemia is prepared for analysis in the laboratory. © University Hospital Dresden/Thomas Albrecht

Media inquiries:
Dr. Anna Kraft
National Center for Tumor Diseases Dresden (NCT/UCC)
Press and Public Relations
Tel.: +49 351 458-5548
Email: anna.kraft@nct-dresden.de
www.nct-dresden.de

Dr. Sibylle Kohlstädt
Deutsches Krebsforschungszentrum (DKFZ)
Strategic Communication and Public Relations
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Fax: +49 6221 42-2968
Email: s.kohlstaedt@dkfz.de
www.dkfz.de

Stephan Wiegand
Staff Unit Public Relations & Marketing
Carl Gustav Carus Faculty of Medicine at Technische Universität Dresden
Tel.: +49 351 458 19389
Fax: +49 351 458 885486
Email: stephan.wiegand@tu-dresden.de
www.tu-dresden.de/med

Holger Ostermeyer
Carl Gustav Carus University Hospital Dresden Press Office
Tel.: +49 351 458-4162
Fax: +49 351 449210505
Email: Pressestelle@uniklinikum-dresden.de www.uniklinikum-dresden.de

Simon Schmitt
Communications and Media Relations | Head and Press Officer
Helmholtz-Zentrum Dresden-Rossendorf
Email: s.schmitt@hzdr.de
Tel.: +49 351 260-3400
www.hzdr.de

National Center for Tumor Diseases Dresden (NCT/UCC)
The National Center for Tumor Diseases Dresden (NCT/UCC) is a joint institution of the German Cancer Research Center, the Carl Gustav Carus Faculty of Medicine at TU Dresden, the Carl Gustav Carus University Hospital Dresden and the Helmholtz-Zentrum Dresden-Rossendorf (HZDR).
The NCT has made it its duty to closely link research and patient care wherever possible. That is why cancer patients at the NCT sites can be treated based on the latest research results. At the same time, the proximity of laboratory and clinic provides researchers with important impulses for their practice-oriented research. The NCT sites share the common goal of developing the NCT into a top international center for patient-oriented cancer research. The Dresden center draws on the structures of the University Cancer Center Dresden (UCC), which was founded in 2003 as one of the first Comprehensive Cancer Centers (CCC) in Germany. Since 2007, the UCC has been honored by the German Cancer Aid e.V. (DKH) as a "Top Oncological Center" on a continuous basis.

German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, identify cancer risk factors and search for new strategies to prevent people from developing cancer. They are developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to all questions on cancer.
Jointly with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, and the Hopp Children's Cancer Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translational centers at seven university partner locations. NCT and DKTK sites combine excellent university medicine with the high-profile research of the DKFZ. They contribute to the endeavor of transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

University Hospital Carl Gustav Carus Dresden
The University Hospital Carl Gustav Carus Dresden offers medical care at the highest level of care. As a full-service hospital, it covers the entire spectrum of modern medicine. The University Hospital combines 20 clinics and outpatient departments, four institutes and ten interdisciplinary centers that collaborate closely with the clinical and theoretical institutes of the Faculty of Medicine.
With 1,295 beds and 160 places for day-care treatment, the Dresden University Hospital is the largest hospital in the city and also the only full-service hospital in eastern Saxony. Around 860 doctors cover the entire spectrum of modern medicine. 1,860 nurses and caregivers ensure the patients' well-being. The medical care of patients suffering from cancer, metabolic and neurodegenerative diseases is an important focus of treatment at the University Hospital.
Germany's largest hospital comparison by the news magazine "Focus" confirms that the University Hospital Carl Gustav Carus Dresden provides an excellent quality of treatment. That is why Dresden's university medicine comes second in the Germany-wide ranking.

Carl Gustav Carus Faculty of Medicine at Technische Universität Dresden
The Dresden University Medicine, consisting of the Carl Gustav Carus Faculty of Medicine and the university hospital of the same name, has specialized in research in the fields of oncology, metabolic as well as neurological and psychiatric diseases. Within these focal areas, the topics of degeneration and regeneration, imaging and technology development, immunology and inflammation, as well as prevention and health care research are of particular interest. International exchange is a prerequisite for top-level research - the Dresden University Medical Center embraces this concept with employees from 73 nations and numerous collaborations with researchers and teams from all over the world.

Helmholtz-Zentrum Dresden-Rossendorf (HZDR)
The Helmholtz-Zentrum Dresden-Rossendorf (HZDR) conducts research in the fields of energy, health and matter. It focuses on the following questions:
•    How can energy and resources be used in an efficient, safe and sustainable way?
•    How can cancer be better visualized, characterized and effectively treated?
•    How do matter and materials react under the influence of strong fields and in smallest dimensions?
To answer these scientific questions, the HZDR operates large infrastructures that are also used by external measurement guests: Ion Beam Center, High Field Magnetic Laboratory Dresden and ELBE Center for High Power Radiation Sources.
The HZDR is a member of the Helmholtz Association, has five sites (Dresden, Freiberg, Grenoble, Leipzig, Schenefeld near Hamburg) and employs almost 1,200 people - about 500 of whom are researchers including 170 PhD students.