MedUni Vienna: Cause of an aggressive form of childhood cancer identified

Anaplastic large cell lymphoma (ALCL) is a very aggressive cancer of the blood, which usually occurs as a tumour in lymph nodes, the skin, the lungs, the liver, and in soft tissue, and mainly affects children and young adults. The cause of this disease has not previously been researched. But now, scientists at the Medical University of Vienna (MedUni Vienna) and the University of Cambridge have, for the first time, succeeded in identifying the origins of ALCL. The results of the study have been published in the leading journal “Nature Communications”.

The current treatment of ALCL mainly consists of intensive chemotherapy, which can lead to severe long-term side effects such as heart disease, infertility and secondary cancers. Up to 40 percent of children diagnosed with ALCL also suffer a relapse, which requires additional chemotherapy.

“The origins of ALCL could be traced to a gene disorder in the development of blood-producing stem cells, which are located in the thymus,” explains Lukas Kenner for the Clinical Institute of Pathology at MedUni Vienna. Scientists believe that in conventional chemotherapy, cancer cells which spread through the body are destroyed, but not the original “cancer stem cells” by which the tumour is produced. As Lukas Kenner, Director of the Institute of Laboratory Animal Pathology at MedUni Vienna and Vetmeduni Vienna, and Deputy Director of the Ludwig Boltzmann Institute for Cancer Research (LBI CR), points out: “This allows them to sow the seeds of a future relapse, which often occurs after the apparently successful completion of treatment.”

Major changes to the immune system play a crucial role
The researchers found that the spread of lymphomas through the body requires a major change of a key part of the immune system, particularly the T-cell receptor (TCR). These are molecules on the surface of the T-cells – a type of white blood cells, which search for viruses and harmful cells in the body. In mice in which ALCL had spread, the TCR was initially required, but was then lost from the surface of the cancer cells. According to Kenner, “This means that the TCR molecule has a strong suppressive effect on tumour development.”

“We now have a better understanding of the origin of this type of lymphoma and the crucial role played by the major changes to the immune system in the spread of this tumour through the body. With this knowledge, we can better combat the cancer genes which are key to the formation and development of lymphomas, and in the future develop new treatments which offer a better possibility of finding a long-term cure,” explains study director Suzanne Turner from the Department of Pathology at the University of Cambridge.

“Current chemotherapy is particularly exhausting for children and adolescents, especially if a relapse occurs and additional treatment is needed. Our new findings about this lymphoma enable the development of more efficient and less toxic medicines, with which every child will soon be able to return to a normal life after treatment,” says Kenner.

Service: Nature Communications
„Anaplastic large cell lymphoma arises in thymocytes and requires transient TCR expression for thymic egress.“ T. Malcolm, P. Villarese, CJ Fairbairn, L. Lamant, A. Tringuand, CE Hook, GA Burke, L. Brugieres, K. Hughes, D. Payet, O. Merkel, A. Schiefer, I. Ashankyty, S. Mian, M. Wasik, M. Turner, L. Kenner, V. Asnafi, E. Macintyre, SD Turner. Nat Commun. 2016 Jan 12;7:10087. doi: 10.1038/ncomms10087.

Five research clusters at MedUni Vienna
A total of five research clusters have been established at MedUni Vienna. Fundamentally, MedUni Vienna focuses on an increasing number of key areas of clinical research. The research clusters include medical imaging, cancer research/oncology, cardiovascular medicine, medical neuroscience and immunology. This study falls into the subject area of clusters for oncology.

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