Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Throwing molecular wrench into gene control machine leads to 'melting away' of leukemia

09.01.2018

Cancer researchers today announced they have developed a way of sidelining one of the most dangerous "bad actors" in leukemia. Their approach depends on throwing a molecular wrench into the gears of an important machine that sets genes into motion, enabling cancer cells to proliferate.

In tests in mice, the newly discovered method has resulted in what the researchers describe as the "melting away" of aggressive blood cancers while at the same time having no harmful impact on the function of normal cells.


By inducing the expression of a small peptide in mouse models of human AML, CSHL researchers were able to prevent MYB, a major cancer enabler, from promoting cancer growth. Imaged 9, 11, and 13 days following introduction of the peptide, mice from the experiments show dramatic differences in outcome. In the left two columns, control (far left) and treated mice in which the peptide was not activated move from pervasive cancer (blue bioluminescence) to terminal (red). Some of the mice did not survive 13 days (blank panel). In contrast, the two right columns show control mice (poor outcomes) and treated mice with the peptide activated (far right). In the latter, in the far right column, one sees the cancer melt away, leaving the treated mice nearly cancer-free.

Credit: Vakoc Lab, CSHL

The new research by Associate Professor Christopher Vakoc and colleagues at Cold Spring Harbor Laboratory (CSHL) is part of a broader effort in Vakoc's lab to fight the often fatal acute myeloid leukemia (AML) by disabling parts of the machinery in cells - called the transcriptional machinery -- that determines when genes are switched on and off.

Central players in this machinery are proteins called transcription factors, thousands of which are active in regulating genes across our chromosomes. The question addressed in the new research, published today in Cancer Cell, was how to target one of the most troublesome transcription factors, called MYB. It's an oncogenic, or cancer-inducing, transcription factor that enables cells to blow through the stop signs that normally prevent out-of-control growth.

"MYB is a dream target in cancer research," says Vakoc, "because it's involved in so many cancers; in leukemia it's special because we know from previous research that by targeting MYB you can get AML not just to stop growing but actually to regress." Deactivating MYB in cancer has been a goal of many research labs..

Yali Xu, a Ph.D. student in the Vakoc lab leading the study, discovered how to selectively take MYB out of the picture in leukemia by throwing a molecular wrench into the mechanism that the transcription factor normally activates. First, the team discovered that MYB activates gene expression by docking at a giant gene-"co-activation" protein called TFIID (pronounced TF-two-D). Next, the they found a tiny weak spot on the massive protein. This Achilles' heel, called TAF12, is a small, nub-like projection. The team then tricked MYB into binding to short protein fragments, or peptides, that are shaped exactly like the place on TAF12 where MYB binds when it is promoting leukemia.

A major achievement in the study was generating this peptide, which acts like a decoy. Experiments in mice that model human AML showed that the peptide finds and binds MYB, preventing it from engaging the TFIID co-activator. This resulted in mouse leukemias shrinking in size by some 80% without causing harm to healthy cells.

While the peptide is not itself a drug, Vakoc says its action could be replicated by a drug. "It's a concept we're now discussing with the pharmaceutical industry. It is going to take lots of work before it can result in a medicine leukemia patients might take. But we're excited about this new approach, because MYB is such an important player in many cancers and until now has eluded efforts to selectively target it."

###

Funding: Cold Spring Harbor Laboratory NCI Cancer Center Support grant; Alex's Lemonade Stand Foundation; Forbeck Foundation; Pershing Square Sohn Cancer Research Alliance; V Foundation; Burroughs-Wellcome Fund Career Award; NIH/NCI; Leukemia & Lymphoma Society Scholar Award.

Citation: Xu, Y et al, "A TFIID-SAGA perturbation that targets MYB and suppresses acute myeloid leukemia." Published online in Cancer Cell January 8, 2017.

About Cold Spring Harbor Laboratory

Founded in 1890, Cold Spring Harbor Laboratory has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. Home to eight Nobel Prize winners, the private, not-for-profit Laboratory employs 1,100 people including 600 scientists, students and technicians. The Meetings & Courses Program annually hosts more than 12,000 scientists. The Laboratory's education arm also includes an academic publishing house, a graduate school and the DNA Learning Center with programs for middle and high school students and teachers. For more information, visit http://www.cshl.edu

Media Contact

Peter Tarr
tarr@cshl.edu
516-367-5055

 @cshl

http://www.cshl.edu 

Peter Tarr | EurekAlert!

More articles from Health and Medicine:

nachricht Scientists discover the basics of how pressure-sensing Piezo proteins work
22.08.2019 | Weill Cornell Medicine

nachricht Protein-transport discovery may help define new strategies for treating eye disease
22.08.2019 | Scripps Research Institute

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Hamburg and Kiel researchers observe spontaneous occurrence of skyrmions in atomically thin cobalt films

Since their experimental discovery, magnetic skyrmions - tiny magnetic knots - have moved into the focus of research. Scientists from Hamburg and Kiel have now been able to show that individual magnetic skyrmions with a diameter of only a few nanometres can be stabilised in magnetic metal films even without an external magnetic field. They report on their discovery in the journal Nature Communications.

The existence of magnetic skyrmions as particle-like objects was predicted 30 years ago by theoretical physicists, but could only be proven experimentally in...

Im Focus: Physicists create world's smallest engine

Theoretical physicists at Trinity College Dublin are among an international collaboration that has built the world's smallest engine - which, as a single calcium ion, is approximately ten billion times smaller than a car engine.

Work performed by Professor John Goold's QuSys group in Trinity's School of Physics describes the science behind this tiny motor.

Im Focus: Quantum computers to become portable

Together with the University of Innsbruck, the ETH Zurich and Interactive Fully Electrical Vehicles SRL, Infineon Austria is researching specific questions on the commercial use of quantum computers. With new innovations in design and manufacturing, the partners from universities and industry want to develop affordable components for quantum computers.

Ion traps have proven to be a very successful technology for the control and manipulation of quantum particles. Today, they form the heart of the first...

Im Focus: Towards an 'orrery' for quantum gauge theory

Experimental progress towards engineering quantized gauge fields coupled to ultracold matter promises a versatile platform to tackle problems ranging from condensed-matter to high-energy physics

The interaction between fields and matter is a recurring theme throughout physics. Classical cases such as the trajectories of one celestial body moving in the...

Im Focus: A miniature stretchable pump for the next generation of soft robots

Soft robots have a distinct advantage over their rigid forebears: they can adapt to complex environments, handle fragile objects and interact safely with humans. Made from silicone, rubber or other stretchable polymers, they are ideal for use in rehabilitation exoskeletons and robotic clothing. Soft bio-inspired robots could one day be deployed to explore remote or dangerous environments.

Most soft robots are actuated by rigid, noisy pumps that push fluids into the machines' moving parts. Because they are connected to these bulky pumps by tubes,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The power of thought – the key to success: CYBATHLON BCI Series 2019

16.08.2019 | Event News

4th Hybrid Materials and Structures 2020 28 - 29 April 2020, Karlsruhe, Germany

14.08.2019 | Event News

What will the digital city of the future look like? City Science Summit on 1st and 2nd October 2019 in Hamburg

12.08.2019 | Event News

 
Latest News

Making small intestine endoscopy faster with a pill-sized high-tech camera

23.08.2019 | Medical Engineering

More reliable operation offshore wind farms

23.08.2019 | Power and Electrical Engineering

Tracing the evolution of vision

23.08.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>