Biallelic disruption of DDX41 activity is associated with distinct genomic and immunophenotypic hallmarks in acute leukemia

Article Oncology

AML with germline DDX41 variants is a clinicopathologically distinct entity with an indolent clinical course and favorable outcome

Peng Li et al.

Summary: The study reveals that DDX41 mutations in AML manifest as male predominance, often lack of family history, indolent course, low proliferative potential, frequent somatic DDX41 mutations, and a favorable overall survival.

LEUKEMIA (2022)

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Article Hematology

Genetic features and clinical outcomes of patients with isolated and comutated DDX41-mutated myeloid neoplasms

Hassan B. Alkhateeb et al.

Summary: DDX41 mutations are associated with late onset myelodysplastic syndromes/acute myeloid leukemia. Patients with these mutations often have an indolent course and comparable overall survival to favorable-risk AML patients.

BLOOD ADVANCES (2022)

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Article Oncology

DDX41 coordinates RNA splicing and transcriptional elongation to prevent DNA replication stress in hematopoietic cells

Satoru Shinriki et al.

Summary: Loss of DDX41 function impairs RNA splicing and leads to DNA replication stress and R-loop formation. DDX41 binds to the splice site of coding RNA, coordinating RNA splicing and transcriptional elongation. Its loss causes splicing impairment and aberrant R-loop formation. These processes may be responsible for disease phenotypes associated with DDX41 mutations.

LEUKEMIA (2022)

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Article Hematology

Molecular and clinical features of myeloid neoplasms with somatic DDX41 mutations

Shiqiang Qu et al.

Summary: DDX41 variants were screened in 47 out of 1529 subjects with myeloid neoplasms, with the most common germline variants being Splice c.935 + 4A>T. The overall response rate to demethylation therapy in DDX41 variants subjects was 69%, with a two-year overall survival rate of 85%.

BRITISH JOURNAL OF HAEMATOLOGY (2021)

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Article Oncology

Next-Generation Sequencing of DDX41 in Myeloid Neoplasms Leads to Increased Detection of Germline Alterations

Sarah A. Bannon et al.

Summary: Previously rare inherited hematologic malignancies are now more frequently identified, particularly with DDX41 mutations predisposing to myeloid neoplasms. Utilizing next-generation sequencing can effectively screen for germline DDX41 mutations, enabling timely care. The majority of patients referred for genetic counseling elected to pursue germline evaluation, with a high confirmation rate of germline DDX41 variants, highlighting the importance of identifying these mutations for appropriate management.

FRONTIERS IN ONCOLOGY (2021)

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Article Cell & Tissue Engineering

Germline DDX41 mutations cause ineffective hematopoiesis and myelodysplasia

Timothy M. Chlon et al.

Summary: DDX41 mutations are common in adult MDS, affecting hematopoietic progenitor cell development and cell cycle, leading to bone marrow failure. While monoallelic DDX41 mutations generally do not impact hematopoiesis, some aged mice may develop MDS features. Biallelic DDX41 mutations have been observed in BM from MDS patients, and may play a role in disease progression in the context of monoallelic DDX41 mutations.

CELL STEM CELL (2021)

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Review Hematology

Clinical features of DDX41 mutation-related diseases: a systematic review with individual patient data

Ziqi Wan et al.

Summary: DDX41 gene mutations are associated with myeloid neoplasms, predominantly affecting older male patients with AML or MDS, showing promising treatment responses. Germline and somatic DDX41 variants possess distinct characteristics, warranting further investigation.

THERAPEUTIC ADVANCES IN HEMATOLOGY (2021)

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Article Multidisciplinary Sciences