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Epitranscriptomic modifications in acute myeloid leukemia: m6A and 2'-O-methylation as targets for novel therapeutic

Cornelius Pauli1,2, Michael Kienhöfer1, Stefanie Göllner1

  • 1Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.

Biological Chemistry
|October 11, 2021
PubMed

Insights

RNA modifications like N6-methyladenosine (m6A) and 2'-O-methylation (2'-O-me) play key roles in cancer. In Acute Myeloid Leukemia (AML), these RNA changes and their enzymes are crucial for disease development and potential therapies.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Oncology

Background:

  • RNA modifications are fundamental biological processes across species.
  • These modifications and their associated enzymes are increasingly linked to human diseases, particularly cancer.
  • Understanding the mechanisms of RNA modifications in disease pathogenesis is rapidly advancing.

Purpose of the Study:

  • To review the current knowledge on RNA modifications in Acute Myeloid Leukemia (AML).
  • To explore the roles of specific RNA modifications, N6-methyladenosine (m6A) and 2 -O-methylation (2 -O-me), in leukemogenesis.
  • To discuss the implications of these findings for potential therapeutic strategies in AML.

Main Methods:

  • Review of existing literature on RNA modifications in AML.
  • Analysis of the roles of key enzymes (writers, erasers, readers) in RNA modification.
  • Examination of the involvement of m6A and 2 -O-me in cancer development.

Main Results:

  • N6-methyladenosine (m6A) modification is a significant modulator of leukemogenesis in AML.
  • Writer proteins METTL3 and METTL14 are implicated in AML pathogenesis and represent potential therapeutic targets.
  • 2 -O-methylation (2 -O-me) of ribosomal RNA is closely linked to leukemogenesis, with roles in AML1-ETO oncofusion protein activity and NPM1 tumor suppressor function.

Conclusions:

  • RNA modifications, including m6A and 2 -O-me, are critical in AML pathogenesis.
  • Specific enzymes and pathways involved in RNA modification offer novel therapeutic targets for AML.
  • Further research into RNA modification mechanisms can uncover new pathogenetic insights and treatment strategies for AML.
Keywords:
2′-O-methylationRNA modificationsacute myeloid leukemiaepitranscriptomem6AsnoRNAs

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