Molecular Characteristics and Clinical Features of Adults with NUP98 Fusions in Acute Myeloid Leukemia

Objective To determine the molecular characteristics and clinical features of patients with nucleoporin 98 (NUP98) fusion gene positive acute myeloid leukemia (AML) and the impact of coexistence of NUP98 fusion genes and other prognosis-related genes. Methods Samples of bone marrow or peripheral blood were collected from the adult patients with de novo AML and myelodysplastic syndrome (MDS) in our hospital from July 1st, 2014 to March 1st, 2017. NUP98 fusuion genes and their karyotype were detected by PCR. The AML patients with chromosome 11p15 rearrangement or NUP98 fusion genes were studied as the research group and the remaining AMLs in this period as the control group. Meanwhile, the control AML group was divided into low-risk, medium-risk and high-risk groups respectively. Through comparison, analyzing the hematological characteristics, CR rates, the frequency of coexpression with other prognosis-related genes, and over all survival were done between these NUP98 fusion gene positive AMLs and control. Results A total of 197 AML patients participated in this study, including 16 (8.1%) having NUP98 fusion genes and the first case of positive NUP98-topoisomerase1 (TOP1) fusion gene. The NUP98 positive AMLs were mainly M2 and M5 in FAB classifications. Fms-like tyrosine kinase-3 (FLT3)-internal tandem duplication (ITD)(FLT3-ITD) occurred31.25% (5/16) and mortality80.00% (4/5) of the patients with NUP98 positive AMLs, higher than control groupoccurred:9.95% (19/181), mortality:42.11% (8/19), P<0.05. The CR rate of the study group induced chemotherapy was 78.57%,higher than the control group and the middle, high and middle rick control group. The median overall survival (OS) and leukemia free survival (LFS) of the patients with NUP98 positive AMLs were 13 months and 5 months, respectively. Conclusion NUP98 fusion positive AMLs have high level of coexistence with other prognostic-related genes, especially FLT3-ITD, leading to poor prognosis, short survival.