Researchers Found Mechanism That Can Help Design Future Therapies -- MEDICA - World Forum for Medicine

Researchers Found Mechanism That Can Help Design Future Therapies

Photo: Graphic of blood cells

Leukaemia is a type of cancer
characterized by an abnormal
increase of white blood cells;
© Steidl

This is a basic research study with potential clinical impact, which was performed, in part, using samples from paediatric leukaemia patients. T-ALL affects mostly children. It is a blood cancer consisting in an uncontrolled growth in the number of T-lymphocytes (white blood cells from the immune system).

The onset of the disease can be triggered by different genetic mutations in genes involved in the proliferation and differentiation of T-cells. The identification and study of mutations found in leukaemia patients is particularly important to help develop more efficient and targeted therapies. Researchers now found a group of mutations that affect 9 percent of the patients with T-ALL and that may originate leukaemia in these patients.

Most importantly, researchers demonstrated that a set of pharmaceutical drugs can eliminate the effect of these mutations, unravelling a potential therapeutic application for their discovery. The current study shows that the mutations occur at the gene coding for a protein localized at the surface of T-cells, the interleukin-7 receptor (IL7R).

This protein contacts with both the exterior and the interior of the cells, acting as a bridge to transfer chemical information from the outside to the inside of cells. Information transfer occurs upon the binding of a bloodstream protein (interleukin-7) to the receptor, which triggers a cascade of cellular reactions that are essential for the correct development and proliferation of T-cells.

In the new study, researchers also found that the mutations promote non-stop, uncontrolled T-cell proliferation, independently of extracellular triggers. This capacity to induce cells to grow relentlessly is associated with the ability to originate tumours.

To help fighting the tumours that contain IL7R mutations, the team of researchers studied pharmaceutical drugs known to act in several steps of the referred cascade of cellular reactions and found that these drugs - which are already being tested against other diseases such as rheumatoid arthritis – can stop cell proliferation induced in mutated cells and promote the elimination of these cells.

Says João T. Barata at Instituto de Medicina Molecular in Lisbon, Portugal: "We discovered that the interleukin-7 receptor, which is essential for proper T-cell development, may also have a "dark side", acting as a Mr. Hyde of sorts. In particular, we found that certain mutations in this gene are involved in paediatric T-cell acute lymphoblastic leukaemia and characterized how they act. Our observations allowed us to identify potential therapeutic weapons against these tumours. Although paediatric acute lymphoblastic leukaemia is among the success stories in cancer therapy, improvements are still needed. We hope our findings will help further increase the efficacy and selectivity of already existing treatments."; Source: Instituto de Medicina Molecular in Lisbon