Abstract
Acute lymphoblastic leukemia is the most common malignancy in children and is characterized by numerous genetic and epigenetic abnormalities. Epigenetic mechanisms, including DNA methylations and histone modifications, result in the heritable silencing of genes without a change in their coding sequence. Emerging studies are increasing our understanding of the epigenetic role of leukemogenesis and have demonstrated the potential of DNA methylations and histone modifications as a biomarker for lineage and subtypes classification, predicting relapse, and disease progression in acute lymphoblastic leukemia. Epigenetic abnormalities are relatively reversible when treated with some small molecule-based agents compared to genetic alterations. In this review, we conclude the genetic and epigenetic characteristics in ALL and discuss the future role of DNA methylation and histone modifications in predicting relapse, finally focus on the individual and precision therapy targeting epigenetic alterations.
Highlights
Leukemia is the most common malignancy in children and adolescents, and is responsible for a third of childhood cancer deaths
Philadelphia chromosome (Ph+) or t(9;22)(q34;q11.2) occurs in 3–5% of childhood B-acute lymphocytic leukemia (ALL) and most patients with chronic myeloid leukemia (CML), which results in BCR-ABL1 fusion gene [24]
Risk stratification of patients with T-Cell Acute Lymphoblastic Leukemia (T-ALL) is largely determined by central nervous system (CNS) status and early response to therapy, which are measured by minimal residual disease (MRD) testing [56]
Summary
Leukemia is the most common malignancy in children and adolescents, and is responsible for a third of childhood cancer deaths. Despite cure rates of ALL exceeding 90% in children, the treatment of relapsed or drugresistant leukemia and some molecular subtypes remains challenging, it is still an important cause of morbidity and mortality in children With such high survival, there is little room for further improvement in outcomes based on increased treatment intensity without unacceptable toxicity. Many of these genetic alterations have important implications for diagnosis and risk-stratification of ALL and for the development of novel and targeted treatments [7]. We focus on the somatic mutational signatures and epigenetic abnormalities of ALL, especially DNA methylations and histone modifications, summarize and discuss the role of epigenetic alterations in predicting relapse and targeted therapy.
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