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Letters to the Editor
patients who had a 5-year event-free survival of 47.0% ± 2.1% (P=0.005), overall survival of 63.7% ± 2.1% (P≤0.001), and a relapse risk of 42.5 ± 2.3 (P=0.002) (Figure 1A-C). Previously described NUP98-NSD1+ cases had similar outcomes to NUP98-KDM5A+ patients cases, with a 5-year event-free survival rate of 22.2% ± 6.9% and an overall survival rate of 45.7% ± 8.7%.7,9 Based on multivariable analysis, NUP98-KDM5A was an inde- pendent risk factor for poor overall survival and relapse, with hazard ratios of 1.77 for overall survival (P=0.009) and 1.62 for relapse risk (P=0.049), but not for event-free survival (hazard ratio 1.40, P=0.08) (Online Supplementary Table S2). Seven NUP98-KDM5A+ patients underwent HSCT in first complete remission. Among these patients, five relapsed and four subsequently died.
Gene expression analysis using RNA-sequencing data from 1,035 patients, including 16 with NUP98-KDM5A+ and 49 with NUP98-NSD1+ , revealed 2,252 differentially
expressed genes between NUP98-KDM5A+ and NUP98- KDM5A− cases, of which 1,542 were upregulated genes (Online Supplementary Table S3). However, hierarchical clustering did not cluster the majority of NUP98- KDM5A+ cases together, but scattered them among sam- ples with normal and other karyotypes (Figure 1D).
The top upregulated genes included many HOXB genes (Online Supplementary Table S3). The upregulation of both HOXA and HOXB genes has been previously reported in NUP98-rearranged cases, and represents a common path- way to leukemia development, as it is also shared with NPM1-mutated AML, t(8;16)-rearranged AML, and oth- ers.7,11 HOXA/B-gene-based principle coordinate analysis, excluding patients with rare or unknown driving aberra- tions, revealed several subgroups (Figure 1E). NUP98-KDM5A clustered together with NPM1-mutated cases and DEK-NUP214, while NUP98-NSD1 clustered separately. The difference between NUP98-KDM5A and
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haematologica | 2021; 106(2)