The Role of CREBBP/EP300 and Its Therapeutic Implications in Hematological Malignancies
1
Department of Hematology, The Second Xiangya Hospital, Molecular Biology Research Center, School of Life Sciences, Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, Changsha 410011, China
2
The Affiliated Nanhua Hospital, Department of Clinical Laboratory, Hengyang Medical School, University of South China, Hengyang 421001, China
*
Authors to whom correspondence should be addressed.
Cancers 2023, 15(4), 1219; https://doi.org/10.3390/cancers15041219
Submission received: 6 January 2023
/
Revised: 6 February 2023
/
Accepted: 7 February 2023
/
Published: 14 February 2023
(This article belongs to the Special Issue New Insights in Molecular Pathology of Cancers: From Biomarkers to Therapeutic Targets)
Simple Summary
Through their regulatory effects on gene expression, histone acetyltransferases have been implicated in the normal physiological activities and genesis of cancer. Genetic aberrations of CREBBP/EP300 have been observed in various types of solid tumors and hematologic malignancies, making them serve as promising therapeutic targets. Here, this review discusses the critical role of CREBBP/EP300 in normal hematopoiesis and also provides a comprehensive overview of how they contribute to the genesis and progression of hematologic malignancies. The impact of different CREBBP/EP300 inhibitors and histone deacetylase inhibitors on targeting therapeutic potential, alleviating chemotherapy resistance, and enhancing immunotherapeutic potential has also been reviewed.
Abstract
Disordered histone acetylation has emerged as a key mechanism in promoting hematological malignancies. CREB-binding protein (CREBBP) and E1A-binding protein P300 (EP300) are two key acetyltransferases and transcriptional cofactors that regulate gene expression by regulating the acetylation levels of histone proteins and non-histone proteins. CREBBP/EP300 dysregulation and CREBBP/EP300-containing complexes are critical for the initiation, progression, and chemoresistance of hematological malignancies. CREBBP/EP300 also participate in tumor immune responses by regulating the differentiation and function of multiple immune cells. Currently, CREBBP/EP300 are attractive targets for drug development and are increasingly used as favorable tools in preclinical studies of hematological malignancies. In this review, we summarize the role of CREBBP/EP300 in normal hematopoiesis and highlight the pathogenic mechanisms of CREBBP/EP300 in hematological malignancies. Moreover, the research basis and potential future therapeutic implications of related inhibitors were also discussed from several aspects. This review represents an in-depth insight into the physiological and pathological significance of CREBBP/EP300 in hematology.
Keywords:
CREBBP; EP300; acetylation; hematological malignancy; chemoresistance; immunotherapy
