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 New nanomedicine slips through the cracks
24.04.2019 | University of Tokyo

nachricht Sugar entering the brain during septic shock causes memory loss
23.04.2019 | Rensselaer Polytechnic 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: Full speed ahead for SmartEEs at Automotive Interiors Expo 2019

Flexible, organic and printed electronics conquer everyday life. The forecasts for growth promise increasing markets and opportunities for the industry. In Europe, top institutions and companies are engaged in research and further development of these technologies for tomorrow's markets and applications. However, access by SMEs is difficult. The European project SmartEEs - Smart Emerging Electronics Servicing works on the establishment of a European innovation network, which supports both the access to competences as well as the support of the enterprises with the assumption of innovations and the progress up to the commercialization.

It surrounds us and almost unconsciously accompanies us through everyday life - printed electronics. It starts with smart labels or RFID tags in clothing, we...

Im Focus: Energy-saving new LED phosphor

The human eye is particularly sensitive to green, but less sensitive to blue and red. Chemists led by Hubert Huppertz at the University of Innsbruck have now developed a new red phosphor whose light is well perceived by the eye. This increases the light yield of white LEDs by around one sixth, which can significantly improve the energy efficiency of lighting systems.

Light emitting diodes or LEDs are only able to produce light of a certain colour. However, white light can be created using different colour mixing processes.

Im Focus: Quantum gas turns supersolid

Researchers led by Francesca Ferlaino from the University of Innsbruck and the Austrian Academy of Sciences report in Physical Review X on the observation of supersolid behavior in dipolar quantum gases of erbium and dysprosium. In the dysprosium gas these properties are unprecedentedly long-lived. This sets the stage for future investigations into the nature of this exotic phase of matter.

Supersolidity is a paradoxical state where the matter is both crystallized and superfluid. Predicted 50 years ago, such a counter-intuitive phase, featuring...

Im Focus: Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter

  • Coolest and smallest star to produce a superflare found
  • Star is a tenth of the radius of our Sun
  • Researchers led by University of Warwick could only see...

Im Focus: Quantum simulation more stable than expected

A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.

Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

Fraunhofer FHR at the IEEE Radar Conference 2019 in Boston, USA

09.04.2019 | Event News

 
Latest News

High-efficiency thermoelectric materials: New insights into tin selenide

25.04.2019 | Materials Sciences

Salish seafloor mapping identifies earthquake and tsunami risks

25.04.2019 | Earth Sciences

Using DNA templates to harness the sun's energy

25.04.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>