A group of researchers from the Institut de recherches cliniques de Montréal (IRCM) and the Essen University Hospital in Germany discovered a new biomarker that could contribute to identifying high-risk patients suffering from an aggressive blood cancer known as acute myeloid leukemia. This new biomarker will help guide patients towards a more effective treatment.
The research was conducted by Tarik Möröy, PhD, Director of the IRCM’s Hematopoiesis and Cancer research unit and Full Research Professor at the Université de Montréal, and Cyrus Khandanpour, MD, hemato-oncologist and clinical researcher at the Essen University Hospital and also visiting scientist at the IRCM. A number of other university hospitals in Germany and the United States also participated in the study.
Improving the 20-per-cent survival rate
Acute myeloid leukemia (AML) is a type of cancer that originates from the bone marrow’s white blood cells. The Canadian Cancer Society reports that, each year, over 1,000 Canadians are diagnosed with this serious disease. Currently, eight out of ten patients die from this type of leukemia.
Dr. Möröy and Dr. Khandanpour’s research helped identify an aggressive form of AML through the presence of a white blood cell protein named GFI1. “We found that patients who show below-average levels of GFI1 in their leukemic cells were much less likely to survive more than five years following their diagnosis,” says Dr. Khandanpour.
From the lab to the patient
Following this finding, the researchers carried out in vitro tests on mouse models and cells from patients diagnosed with this type of leukemia.
“Our genomic analysis of the mice indicated that low GFI1 rates cause epigenetic changes, which influence the selected treatment,” explains Dr. Möröy. “This, in turn, could help quickly guide patients towards more targeted and specific treatments, thus increasing their chances of survival.”
“For AML patients showing reduced levels of GFI1, cells respond poorly to histone deacetylase (HDAC) inhibitors, a treatment used to treat leukemia,” says Judith Hönes, first author of this study and PhD student. “It would therefore be pointless to administer the inhibitors in these specific cases.”
“However, these cells react very well to another treatment using histone acetyltransferase (HAT) inhibitors,” adds Lacramioara Botezatu, the study’s second co-author.
These observations were then correlated with data from patients of several university clinics in the United States and Germany. “The study therefore provides a glimmer of hope for patients with this disease,” explains Tarik Möröy.
“This collaboration between basic and clinical researchers proved to be very successful, so we intend to repeat this type of co-operation in the future,” say Tarik Möröy and Cyrus Khandanpour.
The Quebec-German team hopes the outcome of this study will help investigate more direct impacts on patients. “In a few years, we hope to launch a clinical trial to validate these results,” concludes the research team. “Our team would be very pleased if this research could lead to better treatments for patients with this type of leukemia.”
About the study
This study received financial support from the Canadian Institutes of Health Research (CIHR), the Canada Research Chairs Program, the Leukemia & Lymphoma Society, and the German Cancer Foundation (Deutsche Krebshilfe). The IRCM research staff who participated in the study are Anne Helness, PhD, Charles Vadnais, PhD, and Jennifer Fraszczak, PhD, from the Hematopoiesis and Cancer research unit, and François Robert, PhD, Director of the Chromatin and Genomic Expression research unit. The article, published in Leukemia, was the result of an international collaboration with the Essen University Hospital, which is an institution of the University Duisburg-Essen and the Technical University of Dresden, both in Germany, as well as the Taussig Cancer Institute in Cleveland.
About Tarik Möröy
Tarik Möröy the IRCM’s President and Scientific Director, as well as Full IRCM Research Professor and Director of the Hematopoiesis and Cancer research unit. He obtained a PhD in biochemistry from the Ludwig-Maximilians University in Munich, Germany. Dr. Möröy is also Full Research Professor in the Department of Microbiology, Infectiology and Immunology at the Université de Montréal (accreditation in biochemistry and molecular medicine), and Adjunct Professor in the Department of Medicine (Division of Experimental Medicine) at McGill University. Dr. Möröy holds the Canada Research Chair in Hematopoiesis and Immune Cell Differentiation.
About the IRCM
The IRCM (Institut de recherches cliniques de Montréal) is a renowned biomedical research institute located in the heart of Montréal's university district. Founded in 1967, it is currently comprised of 35 research units and four research specialized clinics: nutrition, metabolism and atherosclerosis; hypertension; diabetes and obesity as well as rare diseases such as cystic fibrosis and familial hyperlipidemia. The IRCM employs nearly 425 people. It is affiliated with the Université de Montréal, and the IRCM Clinic is associated to the Centre hospitalier de l'Université de Montréal (CHUM). It also maintains a long-standing association with McGill University. The IRCM is funded by the Quebec ministry of Economy, Science and Innovation (Ministère de l’Économie, de la Science et de l’Innovation). For more information, visit www.ircm.qc.ca.
About Cyrus Khandanpour, Judith Hönes, Lacramioara Botezatu, Ulrich Dührsen
Dr. Khandanpour is working as a board certified hematologist/oncologist in the department of Hematology at the West German Cancer Centre. He also directs the experimental leukemia therapy group in the department of hematology. Dr. Dührsen is the Head of the Hematology Department at the West German Cancer Centre. Ms. Hönes is a graduate student in Dr. Khandanpour´s group. Dr. Botezatu is a postdoctoral fellow in Dr. Khandanpour’s group.
About the Essen University Hospital
The Essen University Hospital is a pace setter for first-rate medical services in the Ruhr metropolis in Germany. Here, scientific research is tightly interwoven with medical practice, directly benefitting patients who can be certain that they will receive the latest available therapies. In clinical trials, they receive innovative treatments from which patients elsewhere will not benefit until many years later once they become standard therapies everywhere. The Essen University Hospital is an institution of the University Duisburg-Essen (Universität Duisburg-Essen), a public university in North Rhine-Westphalia, Germany and a member of the new-founded University Alliance Metropolis Ruhr. It was founded on January 1, 2003, as a merger of the Gerhard Mercator University of Duisburg and the University of Essen, both of which were established in 1972. With its twelve departments and more than 30 thousand students, the University Duisburg-Essen ranks among the ten largest German universities. Many international students study at the University Duisburg-Essen and give the cities of Duisburg and Essen an international atmosphere. For more information, visit www.uni-due.de.