CBMR researchers and their collaborators discovered that normal, nonmalignant cells use a protein involved in cell-to-cell communication to foster leukaemia development.
T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive disease that affects mainly children and adolescents, and despite great therapeutic improvements, many patients suffer lifelong sequels while others develop chemotherapeutic-resistant disease relapse and do not survive.
To understand how nonmalignant cells contribute to T-ALL development, CBMR scientists studied proteins known to be involved in cellular communication in the immune system, the lymphotoxin proteins.
The lymphotoxin genes were found to be highly expressed in a large subset of T-ALL patient samples and cell lines, so to study the functional role of lymphotoxin in this disease the researchers used a transgenic mouse model. Like human T-ALL, T-cell leukaemia in these mice also displayed high levels of lymphotoxin expression. More importantly, genetic inactivation of the lymphotoxin-β receptor in the transgenic mouse model not only delayed the initial appearance of malignant cells in the thymus, the organ where disease originates, but also prolonged mouse survival.
Treatment of transgenic mice with a molecule inhibiting lymphotoxin-β receptor delayed T-ALL, so these findings suggest that interfering with lymphotoxin function may be a potential strategy for T-ALL treatment
This study can be consulted here in British Journal of Haematolgy.