| Research Abstract |
We examined the relationships between clinical features and somatic mutations in 20 patients with hematologic malignancies carrying the NUP98 fusion gene, including 13 patients with NUP98-HOXAs, 2 with NUP98-HOXDs and NUP98-DDX10, and one each with NUP98-HOXC11, and NUP98-NSD3. Notably, FLT3-internal tandem duplication(ITD) was found in 9(45%), and KIT, NRAS, KRAS, WT1, IDH1, and IDH2 mutations were found in 4(20%), 4(20%), 2(10%), 8(40%), 2(10%), and 1(5%) patients, respectively. Fourteen patients(88%) had at least one mutation in cell proliferation-related gene(FLT3, KIT, or RAS). Seven(83%) of 9 patients with FLT3-ITD and 2(50%) of 4 patients with NRAS mutations died. These results suggest that a high frequency of cell proliferation gene mutations may contribute to leukemogenesis in NUP98-related leukemia, existence of mutations on the preferential genes strongly suggests that leukemogenesis induced by NUP98-fusions may depend on the mutations on selective genes. While FLT3 or NRAS mutations that were identified at high frequency in the patients with NUP98-fusion genes showed poorer prognosis of the patients with NUP98-fusion leukemia, concomitant existence of KIT, WT1, IDH1, or IDH2 mutations strongly suggest that they may also play pathological roles in the hematological malignancies with NUP98-fusion.
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