International Journal of Hematology

DOI: 10.1007/s12185-017-2260-y Pages: 163-174

Myeloid neoplasms with germline DDX41 mutation

1. SA Pathology, Department of Genetics and Molecular Pathology, Centre for Cancer Biology

2. SA Pathology and University of South Australia, Centre for Cancer Biology

3. University of South Australia, Division of Health Sciences, School of Pharmacy and Medical Sciences

4. University of Adelaide, School of Medicine

5. SA Pathology, Department of Haematology

6. Royal Adelaide Hospital, Department of Haematology

7. SA Pathology, ACRF Cancer Genomics Facility, Centre for Cancer Biology

8. University of Adelaide, School of Biological Sciences

Correspondence to:
Anna L. Brown
Tel: +61 8 8222 3885



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.

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