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Erschienen in: Current Hematologic Malignancy Reports 5/2022

04.07.2022 | Germline Predisposition to Myeloid Neoplasms (M Patnaik, Section Editor)

Germline and Somatic Defects in DDX41 and its Impact on Myeloid Neoplasms

verfasst von: Talha Badar, Timothy Chlon

Erschienen in: Current Hematologic Malignancy Reports | Ausgabe 5/2022

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Abstract

Purpose of Review

While DDX41 mutation (m) is one of the most prevalent predisposition genes in adult myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), most patients do not always present with a family history of MDS/AML. In this review, we will be highlighting epidemiological data on DDX41m, roles of DDX41 in oncogenesis, mechanisms of clonal evolution with somatic DDX41m, and clinical phenotypes and management of MDS/AML in patients harboring DDX41m.

Recent Findings

DDX41 encodes a DEAD-box helicase protein that is considered essential for cell growth and viability. High incidence of myeloid malignancies and other cancers in patients bearing DDX41m suggests that defects in DDX41 lead to loss of a tumor suppressor function, likely related to activities in RNA splicing and processing pathways. Seventy percent of cancer cases with DDX41m are associated with MDS/AML alone. More than 65% of familial cases harbor heterozygous germline frameshift mutations, of which p.D140Gfs*2 is the most common. A somatic DDX41m of the second allele is acquired in 70% of cases, leading to hematological malignancy. Myeloid neoplasms with DDX41m are typically characterized by long latency, high-risk disease at presentation with normal cytogenetics and without any additional molecular markers. Recent reports suggests that a subgroup of these patients have an indolent clinical course and have a better long-term survival compared to favorable or intermediate risk AML.

Summary

Distinct clinical/pathologic features and favorable outcomes in MDS/AML highlight the need for standardized classification and gene specific guidelines that could assist in management decisions in patients with DDX41m.
Literatur
Metadaten
Titel
Germline and Somatic Defects in DDX41 and its Impact on Myeloid Neoplasms
verfasst von
Talha Badar
Timothy Chlon
Publikationsdatum
04.07.2022
Verlag
Springer US
Erschienen in
Current Hematologic Malignancy Reports / Ausgabe 5/2022
Print ISSN: 1558-8211
Elektronische ISSN: 1558-822X
DOI
https://doi.org/10.1007/s11899-022-00667-3

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