Gene Loss Causes Leukemia

Author: VIB (the Flanders Institute for Biotechnology)
Published: 2010/05/17
Topic: Leukemia - Publications List

Page Content: Synopsis - Introduction - Main

Synopsis: Leukemia occurs in various forms one of which is T-cell acute lymphoblastic leukemia (T-ALL).

Introduction

Focus

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 Center for Human Genetics and Jean Soulier of the Hopital 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 treatment.