341P - NUP214 gene rearrangements in leukemia patients: Case series from a single institution

Background

The three most famous NUP214-associated gene rearrangements found in leukemia patients are SET::NUP214, NUP214::ABL1, and DEK::NUP214. Regardless of the NUP214’s partner gene or disease type, one common feature NUP214 rearrangements have in common is their association with resistance to treatment and poor prognosis. However, numerous mouse model experiments have shown that NUP214 rearrangement alone is insufficient for, or at least inefficient at, leukemogenesis. Therefore, identification of concurrent mutations as well as sensitive detection of these fusion genes are important for accurate assessment and tailored management of leukemia patients.

Methods

To identify patients with NUP214 gene rearrangement, RNA sequencing results of diagnostic bone marrow aspirates were retrospectively reviewed. Concurrent targeted next generation sequencing results as well as the patients’ demographics, karyotype, and flow cytometry information were also reviewed.

Results

A total of ten patients harboring NUP214 gene rearrangement were identified, among which four had SET: NUP214, three had DEK: NUP214, and three had NUP214: ABL1. Their diagnosis varied depending on the fusion type. Concurrent gene mutations were found in all ten cases. PFH6 mutations was the most common (5/10) followed by WT1 (3/10), NOTCH1 (3/10), FLT3-ITD (3/10) NRAS (2/10), and EZH2 (2/10). One of these patients was the world’s second case of NUP214: ABL1-positive AML.

Conclusions

We have shown the patient characteristics and concurrent test results of ten NUP214-rearranged leukemia patients. Since these gene rearrangements can serve as potential minimal residual disease markers as well as therapeutic targets, we hope our elucidation of the context in which they were discovered will help future research in regard to tailored monitoring and treatment.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.