Genetics and epigenetics of pediatric leukemia in the era of precision medicine

Abstract

Pediatric leukemia represents a heterogeneous group of diseases characterized by germline and somatic mutations that manifest within the context of disturbances in the epigenetic machinery and genetic regulation. Advances in genomic medicine have allowed finer resolution of genetic and epigenetic strategies that can be effectively used to risk-stratify patients and identify novel targets for therapy. This review discusses the genetic and epigenetic mechanisms of leukemogenesis, particularly as it relates to acute lymphocytic leukemias, the mechanisms of epigenetic control of leukemogenesis, namely DNA methylation, histone modifications, microRNAs, and LINE-1 retroelements, and highlights opportunities for precision medicine therapeutics in further guiding disease management. Future efforts to broaden the integration of advances in genomic and epigenomic science into the practice of pediatric oncology will not only identify novel therapeutic strategies to improve clinical outcomes but also improve the quality of life for this unique patient population. Recent findings in precision therapeutics of acute lymphocytic leukemias over the past three years, along with some provocative areas of epigenetics research, are reviewed here.

16-Year-Old Boy with Pancytopenia Suspected of Hematoblastic Malignancy Acute Lymphoblastic Leukemia and Hyperleukocytosis

“…Splenomegaly and hepatomegaly happen due to the absorption of platelets and lymphocytes in the spleen and liver because of white blood cells. Typically, the spleen reacts by taking it out from the blood (DeRenzo et al, 2018) (Ramos et al, 2018). Along with the research by DeRenzo and Ramos et al, this patient also had splenomegaly, which is visibly enlarged (± 12.76 cm) by the ultrasound.…”

Clinical Value of Serum miRNA in Patients with Acute Promyelocytic Leukemia

“…In recent years, a large number of studies have shown that the cause of leukemia is not only limited to chromosome abnormalities and gene mutations but also closely related to epigenetic and miRNA expression changes [30]. miRNAs not only inhibit the expression of target genes at the posttranscriptional level but also its expression is regulated by epigenetic mechanisms and acts directly or indirectly on key epigenetic enzymes such as DNA methyltransferase (DNMTs) [31].…”

Biology and Therapeutic Properties of Mesenchymal Stem Cells in Leukemia

“…The majority are under 18, with the peak age between two and ten years [ 81 , 82 , 83 ]. Pathophysiologically, ALL results from DNA damage causing the uncontrolled growth of lymphoid cells [ 84 , 85 , 86 ].…”