ASXL1/2 mutations and myeloid malignancies

Edward A. Medina, Caroline R. Delma, Feng Chun Yang

Research output: Contribution to journalReview articlepeer-review

7 Scopus citations


Myeloid malignancies develop through the accumulation of genetic and epigenetic alterations that dysregulate hematopoietic stem cell (HSC) self-renewal, stimulate HSC proliferation and result in differentiation defects. The polycomb group (PcG) and trithorax group (TrxG) of epigenetic regulators act antagonistically to regulate the expression of genes key to stem cell functions. The genes encoding these proteins, and the proteins that interact with them or affect their occupancy at chromatin, are frequently mutated in myeloid malignancies. PcG and TrxG proteins are regulated by Enhancers of Trithorax and Polycomb (ETP) proteins. ASXL1 and ASXL2 are ETP proteins that assemble chromatin modification complexes and transcription factors. ASXL1 mutations frequently occur in myeloid malignancies and are associated with a poor prognosis, whereas ASXL2 mutations frequently occur in AML with t(8;21)/RUNX1-RUNX1T1 and less frequently in other subtypes of myeloid malignancies. Herein, we review the role of ASXL1 and ASXL2 in normal and malignant hematopoiesis by summarizing the findings of mouse model systems and discussing their underlying molecular mechanisms.

Original languageEnglish (US)
Article number127
JournalJournal of Hematology and Oncology
Issue number1
StatePublished - Dec 2022


  • ASXL1/2
  • Epigenetic regulation
  • Hematopoiesis
  • Hematopoietic stem cells
  • His leukemogenesis
  • Myeloid malignancies

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Oncology
  • Cancer Research


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