In studying a mouse model of anaplastic large cell lymphoma (ALCL), investigators may have discovered how the disease develops.
“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,” explained study author Lukas Kenner, MD, of the Medical University of Vienna in Austria.
He and his colleagues found that ALCL began in early thymocytes before T-cell receptor (TCR) β-rearrangement.
And the spread of ALCL required a major change in the TCR. A TCR was required for thymic emigration and peripheral tumor development, but the TCR had to be downregulated for T-cell lymphomagenesis.
In mice in which ALCL had spread, the TCR was initially required but was then lost from the surface of lymphoma cells.
“This means that the TCR molecule has a strong suppressive effect on tumor development,” Dr Kenner said.
He and his colleagues recounted these findings in Nature Communications.
“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 tumor through the body,” said study author Suzanne Turner, PhD, of the University of Cambridge in the UK.
“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.”
“Current chemotherapy is particularly exhausting for children and adolescents, especially if a relapse occurs and additional treatment is needed,” Dr Kenner added.
“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.”
