The preclinic studies in a model in vivo show that the activation of the calcineurine is crucial for the maintenance of the tumoral activity several lymphomas and LAL. The cyclosporine and the FK506 cause the death of the tumoral cells indeed. A clinical trial should quickly begin at the Institute Curie to evaluate the potential of this new therapeutic strategy, and in particular of the FK506, for the treatment of the lymphomas.The lymphomas are tumours of the peripheral lymphoid system which ensures the defense of the organization against the pathogenic agents. They generally develop in the lymphatic ganglia.
One classifies them in two main categories according to the implied cells and the capacity of evolution of the tumour. One thus distinguishes the lymphomas not hodgkiniens which touch nearly 9.000 people in France and belong to cancers of which the frequency increased the most these last years, and the lymphomas of Hodgkin, rarer with 1.300 cases and whose incidence does not evolve/move. If the disease of Hodgkin touches especially young adults, the other lymphomas relate to older subjects.
The lymphomas generally develop starting from the lymphocytes B (1) and in some rarer cases of the lymphocytes T. They are characterized by the malignant proliferation of lymphoid cells which tend to infiltrate all the organization. The lymphocytes accumulate because of their incapacity with autodetruire by apoptose (2), invade the ganglia, spleen then gradually osseous marrow and blood. As osseous marrow is the seat of the hematopoïese (3) adult, this invasion involves a modularly insufficiency. This phenomenon then causes an increasingly weak production of red globules which causes an anaemia, a fall of the immunity involving of the serious infections and a reduction of the plates, at the origin of haemorrhages. The most widespread shapes of cancers in the children until adolescence, also being able to occur in the adults, acute leukaemias lymphoid T (LAL-T) are characterized, as for them, by an uncontrolled proliferation of immature cells T which invade osseous marrow, blood and the central nervous system with the detriment of the normal cells.
The calcineurine “to repair” the lymphocytesThe team “Oncogènes and hematopoietic differentiation” of the UMR 146 CNRS/Institute Curie, directed by Jacques Ghysdael study the various forms of leukemia and the cellular mechanisms leading to their development. It has just shown that the calcineurine is activated in a durable way in the lymphocytes B and T tumoral of the various lymphomas and lymphoid acute leukaemias.
This protein phosphates plays an important part in the normal development of the lymphocytes B and T and also takes part in the activation of these cells during the immunizing answer. The calcineurine, once activated, starts the proliferation of the lymphocytes T via the production of a lymphocytary growth promoter, the interleukine 2. However, the activity of the calcineurine is inhibited by the cyclosporine and FK506, two immunosuppresseurs used in private clinic to prevent the rejection of Clerc's Offices of bodies.
While using models in vivo carrying lymphomas or LAL, researchers CNRS of Institut Curie come to show that the inhibition of the calcineurine by cyclosporine A or the FK506 results in death by apoptose lymphoid cells and a tumoral regression. The calcineurine is thus essential with the maintenance of the tumoral characteristics of the lymphocytes T or B in the lymphomas and LAL, which makes a new therapeutic target of it. These two molecules being already used in private clinic, of the tests therapeutic should quickly start, first of all with the FK506, in order to evaluate their potential on lymphomas not hodgkiniens and lymphomas hodgkiniens. Intermediate results of tolerance and effectiveness are awaited as of the next year.
Nature Medicine, June 2007, vol. 13, p. 736-741