New glimmer of hope discovered in the fight against T-cell lymphomas!

New glimmer of hope discovered in the fight against T-cell lymphomas!

Vienna – A new study by research teams at the Medical University of Vienna and international partners has produced new insights into the role of epigenetic changes in anaplastic large cell lymphoma (ALCL). This aggressive form of T-cell lymphoma often affects children and young adults and is known for its poor prognosis. The results were published in the journal “Leukemia” and show how the enzyme HDAC1 functions as a potential tumor inhibitor.

Lymphomas are a group of malignant diseases of the immune system that predominantly affect the lymphatic system. Among the different types of lymphoma, ALCL plays a particularly aggressive role. In particular, ALK-positive ALCL cases, which have a gene fusion of the ALK gene in 60 to 80 percent of cases, urgently need new therapeutic approaches.

Epigenetic mechanisms and their significance

Epigenetic changes, such as DNA methylation and chromatin structural changes, are essential factors that contribute to the development of cancer. Current research shows that such abnormalities, particularly in regulators of DNA methylation and histone modifiers, shape not only the pathogenesis but also the pathophysiology of malignant lymphomas. A review has revealed that epigenomic abnormalities can directly amplify malignant clones and that hematology is at the forefront of the study of disease epigenetics. [PubMed]

In the specific study, the HDAC inhibitor entinostat was tested in a mouse model. The results suggest that blocking HDAC activity could not only delay the development of lymphoma, but in some cases even prevent it. This could open up new therapeutic opportunities in the fight against ALCL, especially for patients resistant to previous therapies.

Mechanisms of ALK-positive ALCL

The ALK gene is a potent driver oncogene whose rearranged form, the NPM::ALK fusion protein, is present in the majority of cases of ALK-positive ALCL. This gene fusion not only affects DNA repair mechanisms, but also influences cellular metabolism and immune response. NPM::ALK regulates various signaling pathways and thereby orchestrates tumor cell survival by both promoting cell proliferation and inhibiting apoptosis. It also induces epigenetic deregulations that silence tumor-suppressing genes and thus contribute to tumor development. [NCBI]

Genetic silencing of HDAC1 in T cells accelerated tumor development in the mouse models, indicating a protective role for this enzyme. Altered packaging of the genetic material and altered gene activity in T cells strengthen signaling pathways that promote lymphoma development. These findings are crucial for future therapeutic direction in the management of ALCL.

In conclusion, the results of the study show that epigenetic therapies are promising due to the high frequency of abnormalities in DNMT and histone modifiers. Increasing interest in targeted epigenomic treatment could usher in a new era in malignant lymphoma therapy, particularly as researchers continue to bridge gaps between basic and clinical research. [OTS]