Cancers, Vol. 12, Pages 2766: Targeted Inhibition of the NUP98-NSD1 Fusion Oncogene in Acute Myeloid Leukemia
Cancers, Vol. 12, Pages 2766: Targeted Inhibition of the NUP98-NSD1 Fusion Oncogene in Acute Myeloid Leukemia
Cancers doi: 10.3390/cancers12102766
Authors:
Sagarajit Mohanty
Nidhi Jyotsana
Amit Sharma
Arnold Kloos
Razif Gabdoulline
Basem Othman
Courteney K. Lai
Renate Schottmann
Madhvi Mandhania
Johannes Schmoellerl
Florian Grebien
Euan Ramsay
Anitha Thomas
Hans-Peter Vornlocher
Arnold Ganser
Felicitas Thol
Michael Heuser
NUP98-NSD1-positive acute myeloid leukemia (AML) is a poor prognostic subgroup that is frequently diagnosed in pediatric cytogenetically normal AML. NUP98-NSD1-positive AML often carries additional mutations in genes including FLT3, NRAS, WT1, and MYC. The purpose of our study was to characterize the cooperative potential of the fusion and its associated Neuroblastoma rat sarcoma (NRAS) mutation. By constitutively expressing NUP98-NSD1 and NRASG12D in a syngeneic mouse model and using a patient-derived xenograft (PDX) model from a NUP98-NSD1-positive AML patient, we evaluated the functional role of these genes and tested a novel siRNA formulation that inhibits the oncogenic driver NUP98-NSD1. NUP98-NSD1 transformed murine bone marrow (BM) cells in vitro and induced AML in vivo. While NRASG12D expression was insufficient to transform cells alone, co-expression of NUP98-NSD1 and NRASG12D enhanced the leukemogenicity of NUP98-NSD1. We developed a NUP98-NSD1-targeting siRNA/lipid nanoparticle formulation that significantly...
Source: Cancers - Category: Cancer & Oncology Authors: Sagarajit Mohanty Nidhi Jyotsana Amit Sharma Arnold Kloos Razif Gabdoulline Basem Othman Courteney K. Lai Renate Schottmann Madhvi Mandhania Johannes Schmoellerl Florian Grebien Euan Ramsay Anitha Thomas Hans-Peter Vornlocher Arnold Ganser Felicitas Thol Tags: Article Source Type: research
More News: Acute Leukemia | Acute Myeloid Leukemia | Brain | Cancer | Cancer & Oncology | Genetics | Leukemia | Nanotechnology | Neuroblastoma | Neurology | Pediatrics | Sarcomas | Study