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Polycomb complexes in MLL-AF9-related leukemias

Aleksandra Sparavier1, Luciano Di Croce2

  • 1Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Dr. Aiguader 88, Barcelona 08003, Spain; CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Baldiri Reixac 4, Barcelona 08028, Spain. Electronic address: https://twitter.com/ASparavier.

Current Opinion in Genetics & Development
|May 24, 2022
PubMed

Insights

The t(9;11) chromosomal translocation creates the MLL-AF9 fusion gene, driving leukemia in children and adults. Polycomb group proteins are implicated in this process, offering potential therapeutic targets.

Area of Science:

  • Hematology
  • Molecular Biology
  • Oncology

Background:

  • The t(9;11) chromosomal translocation is a key driver in specific leukemia types affecting both children and adults.
  • This translocation results in the MLL-AF9 fusion gene, crucial for leukemia progression.
  • The prognosis for t(9;11)-related leukemia varies with age, ranging from poor in infant ALL to intermediate-high risk in adults.

Purpose of the Study:

  • To review the role of Polycomb group proteins in t(9;11)-related leukemia.
  • To explore the molecular mechanisms involving MLL-AF9 and the super elongation complex (SEC).
  • To highlight potential therapeutic strategies targeting these pathways.

Main Methods:

  • Literature review focusing on MLL-AF9 fusion gene and Polycomb group proteins.
  • Analysis of molecular mechanisms of aberrant gene activation.
  • Synthesis of current research on therapeutic targeting.

Main Results:

  • MLL-AF9 recruits the super elongation complex (SEC), leading to aberrant target gene activation.
  • Polycomb group proteins are increasingly linked to MLL-AF9-driven leukemogenesis.
  • Understanding these interactions is key to developing targeted therapies.

Conclusions:

  • The MLL-AF9 fusion protein and its interaction with SEC are central to t(9;11) leukemia.
  • Polycomb group proteins represent a promising avenue for novel therapeutic interventions.
  • Targeting these pathways could offer new treatment options for patients with t(9;11)-related leukemia.

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