Possible treatment targets found for pre-malignant bone marrow disorders

December 29, 2016, Cincinnati Children's Hospital Medical Center

Cincinnati Children's researchers report in Nature Immunology a new mechanism that controls blood cell function and several possible molecular targets for treating myelodysplasia syndromes (MDS) - a group of pre-malignant disorders in which bone marrow does not produce enough healthy blood cells.

MDS can lead to (AML), a fast-spreading blood cancer that can be deadly if not treated promptly. A research team led by cancer biologist Daniel Starczynowski, PhD, found that overexpression of a protein called TRAF6 in hematopoietic (blood) cells drives the onset of MDS. TRAF6 normally functions as an immune sensor of pathogens, according to the authors, who published their data online Dec. 26.

"We found that TRAF6 overexpression in mouse results in impaired and failure," said Starczynowski, a member of the Division of Experimental Hematology and Cancer Biology at Cincinnati Children's Hospital Medical Center. "Based on our paper, a number of therapeutic approaches can be tested and directed against TRAF6 and other related proteins responsible for MDS."

In testing on laboratory mouse models and human MDS/AML samples, the researchers identified a novel substrate of TRAF6 called hnRNPA1, an RNA binding protein. They also found molecular interactions with Cdc42, a protein that helps regulate cells also implicated in cancer. All of these could be potential treatment targets for cases of MDS triggered by overexpression of TRAF6, according to Starczynowski, who said future studies will test their therapeutic potential in mouse models of MDS.

The researchers were able to identify the new molecular targets by conducting a global proteomic analysis of human leukemia cells. This allowed them to the see entire complement of proteins regulated by TRAF6 in leukemia cells.

Beyond the potential for new therapeutic approaches in treating MDS or AML, the paper revealed a new and critical immune-related function for TRAF6, according to the authors. In response to various pathogens, the protein also regulates RNA isoform expression, an important step in the translation of genetic code into protein and cell formation. In the context of the current study, TRAF6's regulation of RNA isoform expression is important to the function of hematopoietic cells and reveals another dimension to how respond to infection, Starczynkowski said.

Explore further: Scientists identify critical pathway to improve muscle repair

More information: Jing Fang et al, Ubiquitination of hnRNPA1 by TRAF6 links chronic innate immune signaling with myelodysplasia, Nature Immunology (2016). DOI: 10.1038/ni.3654

Related Stories

Scientists identify critical pathway to improve muscle repair

November 30, 2015
Researchers at the University of Louisville have discovered a mechanism involved in skeletal muscle repair that may enable clinicians to boost the effectiveness of adult stem cell therapies for diseases such as muscular dystrophy. ...

Study identifies gene network behind untreatable leukemia and possible treatment target

September 4, 2014
Researchers have identified a genetic/molecular network that fuels a high-risk and aggressive form of Acute Myeloid Leukemia (AML) and its precursor disease Myelodysplastic Syndrome (MDS) – providing a possible therapeutic ...

Chinese herbal treatment shows signs of effectiveness in bone marrow recovery

December 15, 2016
UCLA researchers have found that a Chinese herbal regimen called TSY-1 (Tianshengyuan-1) increased telomerase activity in normal blood cells but decreased it in cancer cells. Telomerase is an enzyme responsible for the production ...

Genetic factors control regenerative properties of blood-forming stem cells

December 5, 2016
Researchers from the UCLA Department of Medicine, Division of Hematology Oncology and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have published two studies that define how key ...

Recommended for you

Researchers identify new way to unmask melanoma cells to the immune system

January 16, 2018
system, which enables these deadly skin cancers to grow and spread.

Immunosuppressive cells in newborns play important role in controlling inflammation in early life

January 15, 2018
New research led by The Wistar Institute, in collaboration with Sun Yat-sen University in China, has characterized the transitory presence of myeloid-derived suppressor cells (MDSCs) in mouse and human newborns, revealing ...

Memory loss from West Nile virus may be preventable

January 15, 2018
More than 10,000 people in the United States are living with memory loss and other persistent neurological problems that occur after West Nile virus infects the brain.

Mould discovery in lungs paves way for helping hard to treat asthma

January 15, 2018
A team at The University of Manchester have found that in a minority of patients they studied, a standard treatment for asthma—oral steroids—was associated with increased levels of the treatable mould Aspergillus in the ...

Fast food makes the immune system more aggressive in the long term

January 12, 2018
The immune system reacts similarly to a high fat and high calorie diet as to a bacterial infection. This is shown by a recent study led by the University of Bonn. Particularly disturbing: Unhealthy food seems to make the ...

Past exposures shape immune response in pediatric acute respiratory infections

January 12, 2018
Acute respiratory tract infections (ARTI) are the leading global cause of death in early childhood, according to the Centers for Disease Control and Prevention (CDC). Lower respiratory tract infections, including bronchiolitis ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.