Clinicopathologic and Molecular Characterization of NUP98-Rearranged Acute Leukemias
Funding: The authors received no specific funding for this work.
Sujata Sajjan and Estelle E. Oertling are Co-first author.
ABSTRACT
Introduction
NUP98 rearrangements are rare in acute leukemias and portend a poor prognosis.
Methods
This study explored clinicopathologic and molecular features of five patients with NUP98 rearranged (NUP98-r) acute leukemias, including three females and two males with a median age of 34 years.
Results
NUP98 fusion partners were associated with distinctive leukemia characteristics and biology. Three patients had NUP98::NSD1-r acute myeloid leukemia (AML, all cytogenetically cryptic and with concomitant FLT3-ITD) and unfavorable prognoses (in two patients), one patient had NUP98::HOXA9-r AML with morphologic and immunophenotypic features resembling acute promyelocytic leukemia, and lastly, one patient had previously underreported NUP98::MLLT1-r B/T mixed phenotype acute leukemia. After a median follow-up of 24.7 months, median overall survival was 30 months and three of five patients (60%) remained in complete remission at the last follow-up.
Conclusion
Our study expands the clinical and molecular spectrum of NUP98-r acute leukemias and recommends FISH testing for NUP98 rearrangement on those leukemia cases without recurrent gene rearrangements and/or normal karyotype followed by molecular confirmation to improve timely diagnosis and clinical management.
Conflicts of Interest
Y.F.M. has received honoraria/consulting fees from BMS, Kura Oncology, BluePrint Medicines, Geron, OncLive and MD Education, VJHemOnc and Medscape Live. Y.F.M. participated in advisory boards and received honoraria from Sierra Oncology, Stemline Therapeutics, Blueprint Medicines, Morphosys, Taiho Oncology, SOBI, Rigel Pharmaceuticals, Geron, Cogent Biosciences and Novartis. Y.F.M. received travel reimbursement from Blueprint Medicines, MD Education, and Morphosys. None of these relationships were related to this work. The other authors declare no conflicts of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
