How to manage patients with germline <i>DDX41</i> variants: Recommendations from the Nordic working group on germline predisposition for myeloid neoplasms
Increasing recognition of germline <i>DDX41</i> variants in patients with hematological malignancies prompted us to provide <i>DDX41</i>-specific recommendations for diagnosis, surveillance, and treatment. Causative germline variants in the <i>DDX41</i> predispose to the development of myeloid neoplasms (MNs), especially myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Almost 3%-5% of all patients with MDS or AML carry a pathogenic or likely pathogenic germline <i>DDX41</i> variant, while half of them acquire a somatic second hit in the other allele. <i>DDX41</i>-associated MNs exhibit unique clinical characteristics compared to other hematological malignancies with germline predisposition: MNs occur mostly at advanced age and follow an indolent clinical course. Male carriers are more prone to develop MDS or AML than females. <i>DDX41</i>-associated MN is often hypoplastic, and the malignancy may be preceded by cytopenias.
Authors
- Maria Creignou (ORCID: https://orcid.org/0000-0002-7629-0871)
- Helena Ågerstam (ORCID: https://orcid.org/0009-0002-8216-3876)
- Mette Klarskov Andersen (ORCID: https://orcid.org/0000-0003-2449-5565)
- Bianca Tesi (ORCID: https://orcid.org/0000-0002-8253-2507)
- Kirsten Grønbæk (ORCID: https://orcid.org/0000-0002-1535-9601)
- Eva Hellström‐Lindberg (ORCID: https://orcid.org/0000-0002-7839-3743)
- Panagiotis Baliakas (ORCID: https://orcid.org/0000-0002-5634-7156)
- Jörg Cammenga (ORCID: https://orcid.org/0000-0001-5573-7542)
- Outi Kilpivaara (ORCID: https://orcid.org/0000-0001-8467-2100)
- Ingunn Dybedal (ORCID: https://orcid.org/0000-0002-3229-3069)
- Klas Raaschou‐Jensen (ORCID: https://orcid.org/0000-0002-4032-6617)
- Asbjørg Stray‐Pedersen (ORCID: https://orcid.org/0000-0002-9168-0878)
- Kirsi Jahnukainen
- Ulla Wartiovaara‐Kautto (ORCID: https://orcid.org/0000-0002-2803-2712)
Institutions
- Uppsala University (SE)
- University of Copenhagen (DK)
- Oslo University Hospital (NO)
- Karolinska University Hospital (SE)
- University of Helsinki (FI)
- Lund University (SE)
- Innlandet Hospital Trust (NO)
- Helsinki University Hospital (FI)
- Odense University Hospital (DK)
- Copenhagen University Hospital (DK)
- Rigshospitalet (DK)
- Karolinska Institutet (SE)
- Helsinki Children's Hospital (FI)
- Skåne University Hospital (SE)
- Cancer Society of Finland (FI)
Publication Details
- Journal
- HemaSphere
- Published
- 2024-08-01
- DOI
- https://doi.org/10.1002/hem3.145
- Citations
- 11
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 5.00
Funders
- Cancerfonden
- Svenska Läkaresällskapet
- Center for Innovative Medicine