Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers identify potential new leukemia drug target

23.10.2015

New treatment options are badly needed for acute myeloid leukemia, a relatively rare form of cancer. The malignancy begins in the bone marrow, and from there can spread rapidly to the bloodstream, depriving the body of the essential blood cells that carry oxygen and fight infections.

Now, new work from a team lead by Rockefeller University researchers has revealed a potential genetic weakness of the disease, offering insights into the molecular mechanisms behind acute myeloid leukemia and suggesting a new target for drug development.


The image shows cancerous mouse bone marrow cells generated by the mutant protein AE, found in 15 percent of acute myeloid leukemia patients. Using AE as an entry point, the researchers found another protein that prompts similar changes in gene activation.

Credit: Laboratory of Biochemistry and Molecular Biology at The Rockefeller University/Nature

Previously, researchers identified a variety of mutations associated with this disease, including a DNA rearrangement found in about 15 percent of patients. The abnormal DNA-binding protein produced as a result of this mutation takes on entirely new functions, dramatically altering a set of genes that are turned on in a cell to promote the cancer. But how this mutation affects these changes has remained mysterious.

In their new work published on October 21 in Genes and Development, the researchers describe how they identified the molecular mechanism behind this gene activation.

The researchers, led by Robert G. Roeder, Arnold and Mabel Beckman Professor and head of Rockefeller's Laboratory of Biochemistry and Molecular Biology, began by searching for proteins that interact with the mutant protein, known as AE, produced by a DNA rearrangement. Their screen identified JMJD1C, an enzyme that removes chemical tags, known as methyl groups, from histones, which are proteins contained in chromosomes. These tags serve as repressive marks, indicating that genes in the associated region should be turned off.

To investigate the relationship between JMJD1C and AE, the team first explored the broader effects of removing JMJD1C. "We found that numerous genes were down-regulated upon loss of JMJD1C, and the set overlaps significantly with the genes that are normally activated by AE," explains first author Mo Chen, a postdoc in Roeder's lab.

The loss of gene expression turns out to have dramatic consequences for the disease. The team found that acute myeloid leukemia cells are addicted to the presence of JMJD1C, and without it they cannot survive. "In fact, these cells were very sensitive to depletion of JMJD1C," says Chen. "We see an increase in apoptosis, a sort of cellular suicide."

The team confirmed that JMJD1C interacts with AE, and demonstrated that the enzyme is required for AE to exert its cancer-promoting effects. But they also found that JMJD1C plays an even a broader role in acute myeloid leukemia, beyond its interaction with AE.

"We were very surprised to find that JMJD1C is required for the proliferation of other acute myeloid leukemia cell lines, which do not have AE, so we looked for other proteins that might be responsible for JMJD1C addiction," says Chen. The team found at least two other proteins that can recruit JMJD1C to target genes in diseased cells that lack AE, fueling leukemia growth.

These results suggest that JMJD1C may play a general role in promoting growth in myeloid leukemias, according to the researchers. "We are excited because this type of general phenomena is an ideal target for drug development," Roeder says.

There are already small molecules that inhibit this class of enzymes. "Our work will facilitate the development of selective inhibitors against JMJD1C, which is a highly promising therapeutic target for multiple types of leukemia," Roeder adds.

Wynne Parry | EurekAlert!

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>