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Decoding m6A RNA methylome identifies PRMT6-regulated lipid transport promoting AML stem cell maintenance

Ying Cheng1, Zhuying Gao1, Tiantian Zhang1

  • 1The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Medical Research Institute, Wuhan University, Wuhan, China; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China.

Cell Stem Cell
|December 27, 2022
PubMed

Insights

This study reveals how N6-methyladenosine (m6A) RNA modifications change during acute myeloid leukemia (AML) development. It identifies protein arginine methyltransferase 6 (PRMT6) as crucial for maintaining leukemia stem cells in AML.

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Molecular Oncology

Background:

  • N6-methyladenosine (m6A) is a dynamic RNA modification involved in various biological processes.
  • The role of the m6A RNA methylome in leukemogenesis is not well understood.

Purpose of the Study:

  • To investigate the dynamics of the m6A methylome during acute myeloid leukemia (AML) development.
  • To identify key molecular players, such as PRMT6, involved in maintaining leukemia stem cells (LSCs).

Main Methods:

  • Comprehensive m6A landscape analysis during AML development.
  • Genetic deletion and pharmacological inhibition of PRMT6 in human and murine models.
  • Investigation of the mechanistic link between PRMT6, IGF2BP2, MFSD2A, and docosahexaenoic acid.

Main Results:

  • Significant changes in the m6A methylome were observed during leukemogenesis.
  • PRMT6 and the m6A reader IGF2BP2 were identified as critical for maintaining LSC function.
  • Inhibition of PRMT6 impaired AML development and LSC function by upregulating MFSD2A expression and docosahexaenoic acid levels.

Conclusions:

  • PRMT6 plays a vital role in AML development and LSC maintenance.
  • The PRMT6-MFSD2A signaling axis represents a potential therapeutic target for AML.
Keywords:
IGF2BP2PRMT6RNA m(6)Aacute myeloid leukemialeukemia stem cells

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