Nav: Home

Putting a brake on leukemia cells

June 09, 2016

Biomarkers play an important role in modern cancer medicine. They are used as tools to diagnose cancers more precisely and to better predict the course of the disease. One marker that is frequently associated with leukemia is a chromosomal abnormality called t(8;21) translocation, in which a part of chromosome 8 connects with chromosome 21. Back in the 1970s, researchers already recognized that in a substantial percentage of patients suffering from acute myeloid leukemia (AML), the transformed cells exhibited this chromosomal abnormality. However, scientific studies also showed that the chromosomal rearrangement alone is not sufficient to cause leukemia. In a research project as part of the German Cancer Consortium (DKTK), researchers at the Department of Internal Medicine 3, Munich University Hospital (LMU), have now discovered a new mutation that promotes the growth of cancer cells. The mutation in the ZBTB7A gene boosts the energy metabolism in the cells. "In healthy cells, the active ZBTB7A gene acts like a parking brake on metabolism," said Philipp Greif, who leads the DKTK Junior Research Group "Pathogenesis of Acute Myeloid Leukemia" at LMU. "If the gene is defective, cancer cells get more energy to use for proliferation." Reversely, the scientists were able to show that the growth rate of leukemia cells can be reduced by genetically modifying the cancer cells in such a way that they produce higher levels of active ZBTB7A. The investigators also observed an indication of the gene's growth-inhibiting effect in the clinic: Leukemia patients in whose cancer cells the gene was transcribed at higher levels had significantly better chances of survival than patients in whom the gene was hardly active or not active at all.

Philipp Greif is one of the clinical researchers at the DKTK who are trying to find new, more targeted approaches in the treatment of cancer patients. "Assessing the course of the disease using genetic markers helps us recommend the right therapy," Greif said. "In some cases, the leukemia may be curable with chemotherapy alone, while in others, subsequent stem cell transplantation is the only chance for the patients to be cured." Using the available sample material at the LMU Laboratory for Leukemia Diagnostics and the collections at the other DKTK sites, the scientists now plan to explore whether the new marker can be used to customize therapies for individual patients.

The discovery is also a promising starting point for developing new approaches toward treating AML patients. "It might be possible to use specially modified glucose molecules to block the energy production process in AML cells," said Luise Hartmann, who is the first author of the study. "Initial clinical trials in other cancers have already shown that these agents are well tolerated by patients" About a quarter of all leukemia patients with the t(8;21) chromosomal abnormality display the mutated ZBTB7A gene. But the scientists also observed a clear link between the gene's activity and the course of the disease in leukemia patients in whose cancer cells no mutations in the ZBTB7A gene were detected. "Therapy with the metabolic inhibitor might therefore work in a wider circle of patients," Greif said. This approach might also become interesting for other types of cancer. ZBTB7A mutations also occur in other cancers, such as in gut cancer.
-end-
Hartmann, L. et. al.: ZBTB7A mutations in acute myeloid leukaemia with t(8;21) translocation. In: Nature Communications (June 2, 2016) D

Funding: This project was supported by the Wilhelm Sander Foundation (2014.162.1) and SFB 1243 "Cancer Evolution" of the German Research Foundation (DFG).

In the German Cancer Consortium (DKTK), the German Cancer Research Center (DKFZ) joins up with universities and university hospitals all over Germany specially designated to clinical oriented cancer research. As DKTK's core center the DKFZ works together with research institutions and hospitals in Berlin, Dresden, Essen/Düsseldorf, Frankfurt/Mainz, Freiburg, Munich, Heidelberg and Tübingen to create the best possible conditions for clinical cancer research. The consortium promotes interdisciplinary research at the interface between basic research and clinical research, as well as clinical trials for innovative treatments and diagnostic methods. Another key focus of the consortium's work is on developing research platforms to speed up the application of personalized cancer treatments and to improve the diagnosis and prevention of cancer. The German Cancer Consortium (DKTK) is a joint long-term initiative involving the German Federal Ministry of Education and Research (BMBF), participating German states and the German Cancer Research Center (DKFZ) and was established as one of six German Health Research Centres (DZGs).

German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

Related Cancer Articles:

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.
Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.
Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.