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[Epigenetic alterations in acute lymphoblastic leukemia].

María Del Pilar Navarrete-Meneses1, Patricia Pérez-Vera1

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Epigenetic modifications like DNA methylation and histone alterations are crucial for childhood acute lymphoblastic leukemia (ALL) development. These changes silence tumor suppressors and deregulate oncogenes, contributing to leukemogenesis alongside genetic factors.

Keywords:
Acute lymphoblastic leukemiaDNA methylationEpigeneticsEpigenéticaExpresión génicaGene expressionHistone modificationsLeucemia linfoblástica agudaMetilación del DNAModificaciones de histonasmiRNAs

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Area of Science:

  • Cancer Biology
  • Epigenetics
  • Pediatric Oncology

Background:

  • Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, primarily driven by genetic alterations.
  • Genetic abnormalities alone are insufficient for complete leukemogenesis, necessitating additional epigenetic modifications.
  • Epigenetic alterations, including DNA methylation, histone modifications, and noncoding RNA regulation, are implicated in ALL.

Purpose of the Study:

  • To review the role of epigenetic modifications in the development and progression of acute lymphoblastic leukemia.
  • To highlight specific epigenetic mechanisms, such as DNA hypermethylation and histone remodeling, in ALL pathogenesis.
  • To underscore the interplay between genetic and epigenetic alterations in pediatric leukemia.

Main Methods:

  • Review of existing literature on genetic and epigenetic alterations in Acute lymphoblastic leukemia.
  • Analysis of studies identifying specific epigenetic modifications like DNA methylation, histone modifications, and miRNA dysregulation in ALL.
  • Examination of the impact of these epigenetic changes on oncogene and tumor suppressor gene expression.

Main Results:

  • DNA hypermethylation in promoter regions is a frequent epigenetic modification in ALL, leading to tumor suppressor gene silencing.
  • Alterations in histone remodeling proteins, including histone deacetylases, acetyltransferases, and methyltransferases, are observed in ALL.
  • Dysregulation of microRNAs (miRNAs) and their target genes contributes to the malignant transformation in ALL.

Conclusions:

  • Epigenetic modifications are key events in leukemogenesis, complementing genetic alterations in the development of ALL.
  • These modifications lead to the deregulation of critical oncogenes (e.g., BLK, WNT5B, WISP1) and tumor suppressors (e.g., FHIT, CDKN2A, CDKN2B, TP53).
  • Understanding epigenetic alterations is vital for comprehending the complex etiology of childhood ALL and developing targeted therapies.