Myeloid neoplasms with germline DDX41 mutation

Jesse J.C. Cheah, Christopher N. Hahn, Devendra Hiwase, Hamish S. Scott, Anna L. Brown

Research output: Contribution to journalReview articlepeer-review

68 Citations (Scopus)


Recently, DDX41 mutations have been identified both as germline and acquired somatic mutations in families with multiple cases of late-onset myelodysplastic syndrome (MDS) and/or acute myeloid leukemia. The majority of germline mutations are frameshift mutations suggesting loss of function with DDX41 acting as a tumor suppressor, and there is a common somatic missense mutation found in a majority of germline mutated tumors. Clinically, DDX41 mutations lead to development of high-risk MDS at an age similar to that observed in sporadic cohorts, presenting a unique challenge to hematologists in recognizing the familial context. Functionally, DDX41 has been shown to contribute to multiple pathways and processes including mRNA splicing, innate immunity and rRNA processing. Mutations in DDX41 result in aberrations to each of these in ways that could potentially impact on tumorigenesis—initiation, maintenance or progression. This review discusses the various molecular, clinical and biological aspects of myeloid malignancy predisposition due to DDX41 mutation and highlights how each of these suggest potential therapeutic opportunities through the use of pathway-specific inhibitors.

Original languageEnglish
Pages (from-to)163-174
Number of pages12
JournalInternational Journal of Hematology
Issue number2
Publication statusPublished or Issued - 1 Aug 2017
Externally publishedYes


  • Acute myeloid leukemia
  • DDX41
  • Germline mutation
  • Myelodysplastic syndrome
  • Myeloid malignancy
  • Predisposition

ASJC Scopus subject areas

  • Hematology

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