The PTPN2 gene plays an important role in hindering the development of T-ALL leukemia
                                                   Researchers from VIB and K.U.Leuven, both in Flanders, Belgium, have discovered a new factor in the development of acute lymphoblastic leukemia, a disease that mainly affects children. In the cells of the patients, the specific  gene PTPN2 ceases to function, causing the cancer cells to survive longer and grow  faster. The study provides genetic and functional evidence for a tumor suppressor role of  PTPN2. The research was carried out in close cooperation with scientists from the Hôpital  Saint-Louis in Paris. Understanding the causes of leukemia is important for the development of new targeted therapies. The results appear in the journal Nature Genetics.


What is leukemia or bone cancer?

In patients with leukemia, the formation of white blood cells in the bone marrow is disrupted. This
makes leukemia patients particularly susceptible to infections, because properly functioning white
blood cells ensure protection against intruders such as viruses and bacteria. In the US alone, every
year around 50.000 adults and children develop leukemia.


T-ALL is caused by interplay of various factors

Leukemia occurs in various forms, one of which is T-cell acute lymphoblastic leukemia (T-ALL). Cells
that normally develop into white blood cells, start to divide in an uncontrolled way, giving rise to a
huge number of immature cells. Until now, few factors have been associated with an increased risk of
developing T-ALL, but it is clear that T-ALL develops when errors occur in several genes
simultaneously. Therefore, it is not only important to identify genes that underlie T-ALL, but also to
unravel what combinations give rise to the disease. This is a crucial element in the development of
future specific combination therapies, promising to be more effective than therapies that focus only on
one target.


PTPN2 has a tumor suppressor role

Maria Kleppe and Jan Cools of VIB-K.U.Leuven, together with Peter Vandenberghe of the Centre for
Human Genetics and Jean Soulier of the Hôpital Saint-Louis in Paris, now identified the gene PTPN2 as
another major player. In the DNA of the cells of some leukemia patients, they noticed that the PTPN2
gene was lost, causing proliferation of the cancerous cells. In addition, PTPN2 was identified as a
negative regulator of the activity of a specific kinase. The study provides genetic and functional
evidence for a tumor suppressor role of PTPN2.


Kinases and phosphatases in cancer development

Beyond the specific findings for T-ALL, this study provides new insights into cancer development in
general. Errors in kinases and phosphatases, enzymes able to switch specific cellular functions on of
and off, have long been known as potential causes of cancer, but this study now shows that when
these errors occur together, the carcinogenic effects can reinforce each other. Furthermore, they can
make the cells more resistant to kinase inhibitors, therapeutic substances currently used for cancer
British researchers from the University of Birmingham recently managed an astounding genetic breakthrough. They were able to identify the gene that controls the average lifespan of the laboratory worm Caenorhabditis elegans (C. elegans). In addition to this, the gene also appears to bear a significant influence on the creature's aging process. The team says that the gene is found in a wide number of animals, including humans, and that transposing the research in people could result in new methods of altering traits related to aging, immunity and resistance.

In the new work, which was sponsored with grant money from the Biotechnology and Biological Sciences Research Council (BBSRC), it was discovered that the DAF-16 gene had the same effects in the close evolutionary relatives of C. elegans, which again raises hopes that the findings could be used in human studies as well. Details of the breakthrough study appear in the April 1 issue of the Public Library of Science's open-access scientific journal PLoS ONE.

“Aging is a process that all organisms experience, but at very different rates. We know that, even between closely related species, average lifespans can vary enormously. We wanted to find out how normal aging is being governed by genes and what effect these genes have on other traits, such as immunity. To do that, we looked at a gene that we already knew to be involved in the aging process, called DAF-16, to see how it may determine the different rates of aging in different species,” explains the leader of the work, UB professor Dr Robin May. Four related worm species were targeted for the new experiments.

“DAF-16 is part of a group of genes that drive the biological processes involved in aging, immunity and responses to physical or environmental stresses. The fact that subtle differences in DAF-16 between species seem to have such an impact on aging and health is very interesting and may explain how differences in lifespan and related traits have arisen during evolution,” May continues.

“Research using model organisms that uncovers the biology underpinning aging gives us the opportunity to understand some of the mechanisms that determine how humans age in a healthy, or at least normal, way. It is very important to develop a good understanding of healthy aging if we are to appreciate what happens to an older person's physiology when they become unwell or experience difficulties with everyday tasks such as recalling memories or moving around. Improving the health span to mirror increases in the lifespan is an important subject of BBSRC research,” adds UB professor Douglas Kell.