New insights into T-cell acute lymphoblastic leukaemia development

May 30, 2017

A research team from the National University of Singapore (NUS) led by Assistant Professor Takaomi Sanda, Principal Investigator from the Cancer Science Institute of Singapore and Department of Medicine at NUS Yong Loo Lin School of Medicine, has provided new insights into the molecular mechanism affecting how genes are produced during normal T-cell development, and contributing to leukaemia formation. Results of the study have been published in the journal Leukemia.

T-cells are a type of white blood cell which develops in the thymus (hence the name T-cell), a primary lymphoid organ. These cells play an indispensable role in the body's cellular defence system. In T-cell (T-ALL), which is a cancer of the , T-cells carry genetic mutations which cause them to multiply uncontrollably. Production of genes during T-cell is strictly controlled by the body. Different genes are turned 'on' and 'off' at various stages of T-cell development, in order to ensure T-cells become fully functional in the immune system.

TAL1 triggers the super-enhancer 'switch'

Specifically, the research team studied the protein TAL1, which is encoded by a cancer causing gene previously found to contribute to the development of T-ALL, and discovered that TAL1 activates a 'molecular switch' called a super-enhancer, which subsequently leads to a cluster of genes called GIMAP being activated. This may result in T-cell precursors growing abnormally and not developing into functional T-cells in the body, leading to the development of T-ALL.

Super-enhancers are regions of DNA that increase production of genes linked to important cellular decisions. They can be sensitive to disturbances and occur frequently at cancer genes. The activation of the super-enhancer induces to be abnormally activated, instead of being strictly controlled.

Asst Prof Sanda said, "Currently, most of the patients with T-ALL are young children. While recent improvements in chemotherapy have significantly boosted cure rates for T-ALL, the introduction of intensive chemotherapy causes both short- and long-term adverse effects. Moreover, there are only a limited number of new drugs with specific activity against malignant T-cells. Moving forward, we are looking into identifying potential therapeutic compounds that inhibits the activation of this super-enhancer. We hope to be able to translate it into meaningful therapies for patients afflicted by T-ALL."

Explore further: Preventing too much immunity

More information: W S Liau et al. Aberrant activation of the GIMAP enhancer by oncogenic transcription factors in T-cell acute lymphoblastic leukemia, Leukemia (2016). DOI: 10.1038/leu.2016.392

Related Stories

Preventing too much immunity

December 27, 2016
Scientists at the Immunology Frontier Research Center (IFReC), Osaka University, Japan, report a new molecular mechanism that could explain the cause of some autoimmune diseases.

Study finds recurrent changes in DNA activate genes, promote tumor growth

March 7, 2017
Genetic mutations can increase a person's cancer risk, but other gene "enhancer" elements may also be responsible for disease progression, according to new research out of Case Western Reserve University School of Medicine. ...

New clues found to immune system's misfiring in autoimmune diseases

June 2, 2016
A person's genetic makeup plays a role in autoimmune diseases such as multiple sclerosis that develop when the body is attacked by its own immune system. But little is known about how immune cells are pushed into overdrive.

'Mysterious' non-protein-coding RNAs play important roles in gene expression

January 12, 2017
In cells, DNA is transcribed into RNAs that provide the molecular recipe for cells to make proteins. Most of the genome is transcribed into RNA, but only a small proportion of RNAs are actually from the protein-coding regions ...

Drug that 'switches off' faulty gene in cancer cells could reverse treatment resistance

January 20, 2017
New insights into a gene linked to the development of blood cancers could help to explain why some patients are resistant to a common drug used in cancer treatment.

Recommended for you

Whole food diet may help prevent colon cancer, other chronic conditions

September 21, 2017
A diet that includes plenty of colorful vegetables and fruits may contain compounds that can stop colon cancer and inflammatory bowel diseases in pigs, according to an international team of researchers. Understanding how ...

New kinase detection method helps identify targets for developing cancer drugs

September 21, 2017
Purdue University researchers have developed a high-throughput method for matching kinases to the proteins they phosphorylate, speeding the ability to identify multiple potential cancer drug targets.

Poliovirus therapy induces immune responses against cancer

September 20, 2017
An investigational therapy using modified poliovirus to attack cancer tumors appears to unleash the body's own capacity to fight malignancies by activating an inflammation process that counter's the ability of cancer cells ...

Scientists restore tumor-fighting structure to mutated breast cancer proteins

September 20, 2017
Scientists at the Virginia Tech Carilion Research Institute have successfully determined the full architecture of the breast cancer susceptibility protein (BRCA1) for the first time. This three-dimensional information provides ...

Brain cancer growth halted by absence of protein, study finds

September 20, 2017
The growth of certain aggressive brain tumors can be halted by cutting off their access to a signaling molecule produced by the brain's nerve cells, according to a new study by researchers at the Stanford University School ...

New clinical trial explores combining immunotherapy and radiation for sarcoma patients

September 20, 2017
University of Maryland School of Medicine researchers are investigating a new approach to treat high-risk soft-tissue sarcomas by combining two immunotherapy drugs with radiation therapy to stimulate the immune system to ...

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.