Clinical and Pathologic Spectrum of DDX41-Mutated Hematolymphoid Neoplasms

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• The gene DDX41 plays a role in RNA helicase activity.
• Mutations in DDX41 have been implicated in certain hematologic malignancies.
• Further characterization of DDX41 mutations is needed to understand their full spectrum.

Purpose of the Study:

• To comprehensively analyze the clinicopathologic features of hematolymphoid neoplasms with DDX41 mutations.
• To identify the full range of hematologic disorders associated with DDX41 alterations.

Main Methods:

• Identification of DDX41 mutations in a large cohort of hematologic disorder cases.
• Review of clinical, genetic, phenotypic, and morphologic data for affected patients.
• Analysis of frequently co-occurring mutations and karyotype abnormalities.

Main Results:

• DDX41 mutations were detected in 1.4% of analyzed cases (20/1371).
• Mutations were found in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and other myeloid and lymphoid neoplasms.
• Morphologic features were heterogeneous and nonspecific; common co-mutations included TET2, DNMT3A, and ASXL1.

Conclusions:

• The spectrum of DDX41-mutated disorders is expanded to include CCUS, T-LGL, and plasma cell disorders.
• Morphologic heterogeneity necessitates DDX41 mutation testing for accurate diagnosis of hematolymphoid neoplasms.