Ann Lab Med.  2024 Jul;44(4):335-342. 10.3343/alm.2023.0301.

NUP214 Rearrangements in Leukemia Patients: A Case Series From a Single Institution

• Choi YJ
• Min YK
• Lee ST
• Choi JR
• Shin S

• KMID: 2557932
• DOI: http://doi.org/10.3343/alm.2023.0301

Abstract

Background
The three best-known NUP214 rearrangements found in leukemia (SET:: NUP214, NUP214::ABL1, and DEK::NUP214) are associated with treatment resistance and poor prognosis. Mouse experiments have shown that NUP214 rearrangements alone are insufficient for leukemogenesis; therefore, the identification of concurrent mutations is important for accurate assessment and tailored patient management. Here, we characterized the demographic characteristics and concurrent mutations in patients harboring NUP214 rearrangements.
Methods
To identify patients with NUP214 rearrangements, RNA-sequencing results of diagnostic bone marrow aspirates were retrospectively studied. Concurrent targeted nextgeneration sequencing results, patient demographics, karyotypes, and flow cytometry information were also reviewed.
Results
In total, 11 patients harboring NUP214 rearrangements were identified, among whom four had SET::NUP214, three had DEK::NUP214, and four had NUP214::ABL1. All DEK::NUP214-positive patients were diagnosed as having AML. In patients carrying SET::NUP214 and NUP214::ABL1, T-lymphoblastic leukemia was the most common diagnosis (50%, 4/8). Concurrent gene mutations were found in all cases. PFH6 mutations were the most common (45.5%, 5/11), followed by WT1 (27.3%, 3/11), NOTCH1 (27.3%, 3/11), FLT3-internal tandem duplication (27.3%, 3/11), NRAS (18.2%, 2/11), and EZH2 (18.2%, 2/11) mutations. Two patients represented the second and third reported cases of NUP214::ABL1-positive AML.
Conclusions
We examined the characteristics and concurrent test results, including gene mutations, of 11 leukemia patients with NUP214 rearrangement. We hope that the elucidation of the context in which they occurred will aid future research on tailored monitoring and treatment.

Keyword

Gene rearrangement; High-throughput nucleotide sequencing; Leukemia; NUP214; Oncogene fusion

Reference

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