TY - JOUR
T1 - Current Understanding of DDX41 Mutations in Myeloid Neoplasms
AU - Kim, Kunhwa
AU - Ong, Faustine
AU - Sasaki, Koji
N1 - Funding Information:
This review was supported by the MD Anderson Cancer Center Support Grant CA016672 from the National Cancer Institute.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/1
Y1 - 2023/1
N2 - The DEAD-box RNA helicase 41 gene, DDX41, is frequently mutated in hereditary myeloid neoplasms, identified in 2% of entire patients with AML/MDS. The pathogenesis of DDX41 mutation is related to the defect in the gene’s normal functions of RNA and innate immunity. About 80% of patients with germline DDX41 mutations have somatic mutations in another allele, resulting in the biallelic DDX41 mutation. Patients with the disease with DDX41 mutations reportedly often present with the higher-grade disease, but there are conflicting reports about its impact on survival outcomes. Recent studies using larger cohorts reported a favorable outcome with a better response to standard therapies in patients with DDX41 mutations to patients without DDX41 mutations. For stem-cell transplantation, it is important for patients with DDX41 germline mutations to identify family donors early to improve outcomes. Still, there is a gap in knowledge on whether germline DDX41 mutations and its pathology features can be targetable for treatment, and what constitutes an appropriate screening/surveillance strategy for identified carriers. This article reviews our current understanding of DDX41 mutations in myeloid neoplasms in pathologic and clinical features and their clinical implications.
AB - The DEAD-box RNA helicase 41 gene, DDX41, is frequently mutated in hereditary myeloid neoplasms, identified in 2% of entire patients with AML/MDS. The pathogenesis of DDX41 mutation is related to the defect in the gene’s normal functions of RNA and innate immunity. About 80% of patients with germline DDX41 mutations have somatic mutations in another allele, resulting in the biallelic DDX41 mutation. Patients with the disease with DDX41 mutations reportedly often present with the higher-grade disease, but there are conflicting reports about its impact on survival outcomes. Recent studies using larger cohorts reported a favorable outcome with a better response to standard therapies in patients with DDX41 mutations to patients without DDX41 mutations. For stem-cell transplantation, it is important for patients with DDX41 germline mutations to identify family donors early to improve outcomes. Still, there is a gap in knowledge on whether germline DDX41 mutations and its pathology features can be targetable for treatment, and what constitutes an appropriate screening/surveillance strategy for identified carriers. This article reviews our current understanding of DDX41 mutations in myeloid neoplasms in pathologic and clinical features and their clinical implications.
KW - acute myeloid leukemia
KW - DDX41 mutations
KW - hereditary myeloid neoplasms
KW - myelodysplastic syndrome
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U2 - 10.3390/cancers15020344
DO - 10.3390/cancers15020344
M3 - Review article
C2 - 36672294
AN - SCOPUS:85146596773
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 2
M1 - 344
ER -