Imagine this scenario on a highway: A driver starts to make a sudden lane change but realizes his mistake and quickly veers back, too late. Other motorists have already reacted and, in some cases, collide. Meanwhile, the original motorist - the one who caused the problem - drives on.
This is similar to what happens with the protein TET2 and a variety of blood cancers. TET2 is a tumor suppressor, preventing hematopoietic (blood) stem cells from overgrowing. However, if TET2 becomes mutated, which happens more frequently than we like, it allows other genes to mutate. TET2 loss does not actually create a cancerous state, but it helps create the conditions for cancer to thrive.
"If you lose TET2, it's not a malignant state, per se," said Mingjiang Xu, M.D., Ph.D., cancer researcher at Sylvester Comprehensive Cancer Center and associate professor of biochemistry and molecular biology at the University of Miami Miller School of Medicine. "But it's creating a situation for other mutations to happen, leading to all types of blood cancer."
Xu and colleagues have been studying Tet2 for several years, and are starting to get a handle on how it operates. They published a paper today in the prestigious journal Nature Communications, which describes how TET2 loss can open the door for mutations that drive myeloid, lymphoid, and other cancers.
A different kind of mutation
That TET2 has a hand in several blood cancers makes it unique. Many mutated genes generate a specific type of cancer, depending on where they originate.
"If you lose TET2, it leads to blood cancers and it could be any type," said Xu. "Usually if you lose one gene, it leads to one specific cancer."
TET2 is an enzyme that demethylates DNA. Methylation turns down genes, keeping them from coding for specific proteins. In other words, TET2 may operate as a master switch, controlling whether certain genes are turned on or off.
TET2 mutations are found in 30 percent of myelodysplastic syndrome (MDS); 30 percent of secondary acute myeloid leukemias; and more than 50 percent of chronic myelomonocytic leukemias.
In the Nature Communications paper, Xu's team showed that mice without the Tet2 gene are more prone to blood cancers. In fact, removing Tet2 turns blood stem cells into mutation machines, and some of those malfunctions generate cancer.
From a clinical standpoint, TET2 is a little tricky. First, it is easier to turn a protein off than turn it on. In addition, TET2 does not actually drive the cancer alone - it's the mutations acquired cooperate with the TET2 loss doing that nasty work. Turning up Tet2 could be helpful, but it has to happen early. Once the mutations are generated, targeting Tet2 would have little effect.
Still, Xu believes TET2 therapeutics could have a place in blood cancer treatment. He notes that around 5 percent of people over the age of 70 have TET2 mutations, which would make them ideal candidates for a preventive therapy.
"We are developing a method to target TET2," said Xu. "If we target that population for early therapy, we could potentially prevent those downstream mutations from happening."
Patrick Bartosch | EurekAlert!
One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie
The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy