Dr. Irmela Jeremias from Helmholtz Zentrum München and her colleagues have succeeded in finding a small population of inactive leukemia cells that is responsible for relapse of the disease. Now the way is paved for research into new therapies that prevent disease relapse by eliminating the remaining, so-called dormant leukemia cells. The research results have now been published in the Cancer Cell journal.
Chemotherapy often fails in leukaemia when resistant cells survive treatment and bring about a relapse of the disease (recurrence). New therapies are therefore needed to eliminate these cells. The team of scientists headed by Jeremias, head of the 'Apoptosis' research group in the Gene Vectors Research Unit (AGV) at the Helmholtz Zentrum München, has now isolated and characterized therapy-resistant cells for the first time. "Previously the biological principles responsible for a relapse in leukaemia were not fully understood," says Jeremias. "Our new approach is to isolate dormant cells, which gives us the first possibility of developing therapies that switch off these cells."
Isolated cells respond to drugs
"We have found a method to dissociate dormant leukaemia cells from their surroundings, where they are safe from attacks by therapeutics," explains Sarah Ebinger, doctoral candidate in the AGV and the article's first author. With the help of modern genetic engineering* and dyes that mark cell growth, the scientists isolated cells and identified a rare cell type that resembled cells triggering relapse. These cells were inactive and resistant to therapy. "We then found out that these cells, once they have been dissolved out of their surroundings, are indeed susceptible to therapy and react well to therapeutics," adds Erbey Özdemir, doctoral candidate in the AGV. "This has brought us a small step closer to the global goal of preventing disease relapse in patients suffering leukaemia," says Jeremias. "It might serve as basis for new therapies that destroy resistant leukaemia cells before they induce relapse."
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Further information
Original publication
Ebinger S. et al. (2016): Characterization of Rare, Dormant, and Therapy-Resistant Cells in Acute Lymphoblastic Leukemia; Cancer Cell, DOI: http://dx.doi.org/10.1016/j.ccell.2016.11.002
The Helmholtz Zentrum München, as the German Research Center for Environmental Health, pursues the objective of developing personalized medicine for the diagnosis, therapy and prevention of widespread diseases such as diabetes mellitus and lung diseases. To this end, it examines the interactions of genetics, environmental factors and lifestyle. The Zentrum's headquarters is located in Neuherberg in the north of Munich. The Helmholtz Zentrum München employs around 2,300 people and is a member of the Helmholtz Association, which has 18 scientific-technical and biological-medical research centres with around 37,000 employees. http://www.helmholtz-muenchen.de
The Gene Vectors Research Unit studies the Epstein-Barr Virus (EBV), a tumour virus in humans, and its contribution to different diseases. The goal is to discover how the immune system in a healthy individual keeps EBV and other human herpes viruses in check and which immune controls fail in patients. The development of tumours of the immune system - lymphoma and leukaemia - is a further area of investigation. Our medium range goal is to develop new drugs, vaccines against EBV, and cell-based therapies in order to efficiently treat or prevent infectious diseases, leukaemia and lymphoma. http://www.helmholtz-muenchen.de/en/agv
Journal
Cancer Cell