Histone deacetylase inhibitors: targeting epigenetic regulation in the treatment of acute leukemia

Ther Adv Hematol. 2024 Oct 16:15:20406207241283277. doi: 10.1177/20406207241283277. eCollection 2024.

Abstract

Acute leukemia (AL) is a rare yet perilous malignancy. Currently, the primary treatment for AL involves combination chemotherapy as the cornerstone of comprehensive measures, alongside hematopoietic stem cell transplantation as a radical approach. However, despite these interventions, mortality rates remain high, particularly among refractory/recurrent patients or elderly individuals with a poor prognosis. Acetylation, a form of epigenetic regulation, has emerged as a promising therapeutic avenue for treating AL. Recent studies have highlighted the potential of acetylation regulation as a novel treatment pathway. Histone deacetylase inhibitors (HDACis) play a pivotal role in modulating the differentiation and development of tumor cells through diverse pathways, simultaneously impacting the maturation and function of lymphocytes. HDACis demonstrate promise in enhancing survival rates and achieving a complete response in both acute myeloid leukemia and acute T-lymphoblastic leukemia patients. This article provides a comprehensive review of the advancements in HDACi therapy for AL, shedding light on its potential implications for clinical practice.

Keywords: acute leukemia; histone deacetylase inhibitors.

Plain language summary

Histone deacetylase inhibitors represent a method of treating acute leukemia by targeting DNA acetylation to regulate genetic information without altering the DNA sequence Acute leukemia (AL) is a rare yet perilous malignancy. Presently, the primary treatments for AL encompass combination chemotherapy as the cornerstone of a comprehensive approach, and hematopoietic stem cell transplantation (HSCT) as a radical treatment. However, despite these interventions, mortality rates remain elevated, particularly among refractory/relapsing patients or older adults with a grim prognosis. Epigenetic regulation entails altering the expression of genes through pertinent genetic information without modifying the DNA sequence. Acetylation modification, as a form of epigenetic regulation, has emerged as a promising avenue for AL treatment. Recent studies have underscored the potential of acetylation regulation as a novel therapeutic approach. Histone deacetylase inhibitors (HDACis) modulate the differentiation and development of tumor cells through various mechanisms and impact the maturation and function of lymphocytes. HDACis exhibits promise in enhancing survival rates for acute leukemia, among other benefits. This article offers a comprehensive review of the advancements in HDACis therapy for AL, shedding light on its potential implications for clinical practice.

Publication types

  • Review