Ann Lab Med.  2025 Jan;45(1):53-61. 10.3343/alm.2024.0190.

Rare Non-Cryptic NUP98 Rearrangements Associated With Myeloid Neoplasms and Their Poor Prognostic Impact

• Park MS
• Kim B
• Jang JH
• Jung CW
• Kim HJ
• Kim HY

• KMID: 2563855
• DOI: http://doi.org/10.3343/alm.2024.0190

Abstract

Background
NUP98 rearrangements (NUP98r), associated with various hematologic malignancies, involve more than 30 partner genes. Despite their clinical significance, reports on the clinicopathological characteristics of rare NUP98r remain limited. We investigated the characteristics of patients with myeloid neoplasms harboring NUP98r among those identified as having 11p15 translocation in chromosomal analysis.
Methods
We retrospectively reviewed results from bone marrow chromosomal analyses conducted between 2011 and 2023 and identified 15 patients with 11p15 translocation. Subsequently, NUP98r were evaluated using FISH and/or reverse transcription PCR, and clinical and laboratory data of the patients were analyzed.
Results
NUP98r were identified in 11 patients initially diagnosed as having AML (N = 8), myelodysplastic syndrome (N = 2), or chronic myelomonocytic leukemia (N = 1), with a median age of 44 yrs (range, 4–77 yrs). Three patients had a history of chemotherapy. In total, five NUP98 fusions were identified: NUP98::DDX10 (N = 3), NUP98::HOXA9 (N = 2), NUP98::PSIP1 (N = 2), NUP98::PRRX1 (N = 1), and NUP98::HOXC11 (N = 1). Patients with NUP98r exhibited a poor prognosis, with a median overall survival of 12.0 months (95% confidence interval [CI], 3.4–29.6 months) and a 5-yr overall survival rate of 18.2% (95% CI, 5.2%–63.7%).
Conclusions
Our study revealed the clinical and genetic characteristics of patients with myeloid neoplasms harboring rare and non-cryptic NUP98r. Given its association with poor prognosis, a comprehensive evaluation is crucial for identifying previously underdiagnosed NUP98r in patients with myeloid neoplasms.

Keyword

Gene fusion; Hematologic neoplasms; NUP98; Prognosis; Translocation; 11p15

Figure

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  Fig. 1 Representative FISH and molecular analysis results for various NUP98r. (A) FISH analysis using a NUP98 break-apart probe showed negative (two fusions) and positive (one red, one green, and one fusion) signals in case No. 11. (B) Agarose gel electrophoresis of fusion transcripts between NUP98 and each partner gene (lane 1, internal control using GAPDH [amplicon size, 131 bp], lane 2, fusion transcripts using primer pairs of NUP98 and partner genes). (C) Confirmation of the breakpoint of each fusion transcript via Sanger sequencing. Abbreviation: NUP98r, NUP98 rearrangement.

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  Fig. 2 Kaplan–Meier plot showing the survival probability of patients with NUP98r and other AML subgroups. Abbreviations: AML-NK, AML with normal karyotype; AML-MR, AML with myelodysplasia-related; AML-mutated TP53, AML with mutated TP53.

Reference

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