06:44am Friday 05 June 2020

A new therapeutic target identified for the most widespread cutaneous lymphoma

The study, published in the Journal of Investigative Dermatology, was co-led by Fernando Gallardo, a dermatologist at the Hospital del Mar and a researcher in the translational research group on haematopoietic malignancies at the Hospital del Mar Medical Research Institute (IMIM); Luis Espinosa and Anna Bigas from the IMIM Cancer Stem Cells Laboratory; Juan Sandoval, researcher at the La Fe Research Institute (IISlaFe); and Ángel Diaz, researcher at the Bellvitge Biomedical Research Institute (IDIBELL). The project was conducted with a series of skin samples from patients with mycosis fungoide in tumour phase and led to the identification of the miR-200C molecule as a possible therapeutic target for designing future treatments for this disease.

Mycosis fungoide is a malignant disease that starts on the skin, in which some of the blood cells responsible for the human immune system –T cell lymphocytes– become malignant and accumulate on the skin. Later and on some patients, the cells develop new mechanisms for invading extracutaneous and visceral tissues, which necessitates an aggressive clinical course and may even lead to the death of the patient. The study centred on the Notch pathway, a family of transmembrane receptors that regulate, among other processes, T lymphocyte differentiation and maturation. This pathway is involved in the progression of different forms of cutaneous T cell lymphomas, such as mycosis fungoide. “The purpose of this project has been to research the state of the Notch pathway in a series of samples from patients with mycosis fungoide and compare the results to a control group to discover if Notch activation in tumours is influenced by epigenetic modifications”, explains Dr Gallardo.

DNA methylation is one of these epigenetic mechanisms that changes gene expression without modifying the DNA. Methylation plays a central role in the coordination of gene transcription in normal healthy cells, but when it is altered it contributes to the onset and progression of cancer. Researchers studied methylation patterns in several components of the Notch pathway and confirmed that Notch1 –one of the molecules that forms part of the Notch receptor family– is activated in samples of patients with mycosis fungoide.

The next step in the study was to decode how the Notch signalling pathway is activated. “Our results indicate that the miR-200C molecule is epigenetically repressed in samples of patients with tumours and that this repression leads to the activation of the Notch pathway”, explains Luis Espinosa, coordinator of the research group on molecular mechanisms of cancer and stem cells at IMIM and the last author of the article.

These results open up doors to new strategies for treating this type of cancer. “The restoration of miR 200C expression, silenced in the tumour cells, could represent a potential therapeutic target for this subtype of lymphomas “, states Fernando Gallardo.

Mycosis fungoide is the most frequent form of cutaneous T cell lymphoma. The incidence of the disease increases with age, where 50 is the average age at which it tends to appear. The symptoms initially manifest on the skin, where they remain for years and even decades. In more advanced stages, it tends to affect the lymph nodes and internal organs and can even cause the death of patients.


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