Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies

Hematologic malignancies are one of the most common cancers, and the incidence has been rising in recent decades. The clinical and molecular features of hematologic malignancies are highly heterogenous, and some hematologic malignancies are incurable, challenging the treatment, and prognosis of the patients. However, hematopoiesis and oncogenesis of hematologic malignancies are profoundly affected by epigenetic regulation. Studies have found that methylation-related mutations, abnormal methylation profiles of DNA, and abnormal histone deacetylase expression are recurrent in leukemia and lymphoma. Furthermore, the hypomethylating agents and histone deacetylase inhibitors are effective to treat acute myeloid leukemia and T-cell lymphomas, indicating that epigenetic regulation is indispensable to hematologic oncogenesis. Epigenetic regulation mainly includes DNA modifications, histone modifications, and noncoding RNA-mediated targeting, and regulates various DNA-based processes. This review presents the role of writers, readers, and erasers of DNA methylation and histone methylation, and acetylation in hematologic malignancies. In addition, this review provides the influence of microRNAs and long noncoding RNAs on hematologic malignancies. Furthermore, the implication of epigenetic regulation in targeted treatment is discussed. This review comprehensively presents the change and function of each epigenetic regulator in normal and oncogenic hematopoiesis and provides innovative epigenetic-targeted treatment in clinical practice.

Automated summary

Hematologic malignancies are common and incurable cancers that have been increasing in incidence. The epigenetic regulation, including DNA modifications, histone modifications, and noncoding RNA-mediated targeting, plays a vital role in hematologic oncogenesis. Abnormal methylation profiles and histone deacetylase expression are frequently found in leukemia and lymphoma. Hypomethylating agents and histone deacetylase inhibitors have shown effectiveness in treating certain hematologic malignancies. This review comprehensively discusses the role of epigenetic regulators in normal and oncogenic hematopoiesis and their implications in targeted treatment.