HDAC1 Enzyme Acts as a Tumor Suppressor in Aggressive T-Cell Lymphomas

Recent research has uncovered a vital role for the enzyme HDAC1 in the development and progression of aggressive T-cell lymphomas, particularly anaplastic large cell lymphoma (ALCL), a rare form of non-Hodgkin's lymphoma. This disease primarily affects children and young adults and is characterized by rapid progression and resistance to conventional treatments.

Lymphomas are cancers originating from the lymphatic system's cells, with ALCL being one of the more aggressive subtypes. The study, conducted by a collaboration of institutions including the Medical University of Vienna, the European Institute of Oncology in Turin, Boston Children's Hospital, Harvard Medical School, and the University of Cambridge, has shed light on the epigenetic mechanisms underlying this disease.

Epigenetic changes, which influence gene expression without altering the underlying DNA sequence, play a significant role in many cancers. In particular, modifications involving DNA methylation and chromatin structure are key factors. The research focused on histone deacetylases (HDACs), a family of enzymes that regulate gene activity by modifying chromatin accessibility.

Using mouse models and human lymphoma cells, the team explored the effects of HDAC inhibition, specifically testing the drug entinostat, an HDAC inhibitor currently in clinical trials. They found that blocking HDAC activity delayed lymphoma onset and, in some cases, prevented tumor development. These promising results extended to lymphoma cells resistant to other therapies, suggesting potential for such drugs in resistant cases.

Surprisingly, the genetic silencing of HDAC1 in T cells accelerated tumor growth in the mouse model. This indicates that HDAC1 has a protective function during certain stages of lymphoma development, a role that was previously underestimated. Molecular analysis revealed that loss of HDAC1 disrupted normal chromatin packaging and altered signaling pathways like PDGFRB-STAT5 and T cell receptor-mediated mechanisms, which may promote lymphoma progression.

According to study lead Gerda Egger, this research provides hope for expanding treatment options for ALK-positive ALCL, especially in cases that develop resistance to current therapies. The findings also support the potential use of HDAC inhibitors as an additional therapeutic strategy.

Overall, this study underscores the complex role of epigenetic factors in lymphoma and highlights the importance of considering the protective functions of enzymes like HDAC1 when developing targeted treatments. It also opens new avenues for the clinical application of epigenetic drugs in combating aggressive T-cell lymphomas.

Source: MedicalXpress