Nov 22, 2019 · Together, these findings indicate that CRM1 acts as a key molecule that connects leukemogenic proteins to aberrant HOX gene regulation either via nucleoporin-CRM1 interaction (for SET-Nup214) or NES-CRM1 interaction (for NPM1c).

We demonstrate that NPM1c directly regulates oncogenic gene expression in collaboration with the MLL1 complex and define the mechanism by which MLL1-Menin small molecule inhibitors produce clinical responses in patients with NPM1 -mutated AML.

Blocking CRM1-mediated nuclear export of such proteins is a novel therapeutic strategy to restore tumor suppressor function. Orally bioavailable selective inhibitors of nuclear export (SINE) that irreversibly bind to CRM1 and block the function of this protein have been recently developed.

Nucleophosmin (NPM1) is a critical cellular protein that has been implicated in a number of pathways including mRNA transport, chromatin remodeling, apoptosis and genome stability. NPM1 function is a critical requirement for normal cellular biology ...

Nov 22, 2019 · Collectively these results demonstrate that CRM1 creates a platform on the HOX cluster regions to recruit the leukemogenic proteins, either via nucleoporin-CRM1 (Nup98- or Nup214-fusions to CRM1) interaction or NES-CRM1 (NPM1c to CRM1) interaction, to induce aberrant expression of HOX genes .

Dec 17, 2024 · NPM1 also contains 2 N-terminal nuclear export signal (NES) motifs that drive its nuclear export via interaction with the nuclear exporter XPO1 (CRM1) [3].

Aug 4, 2024 · CRM1 is best known for its role in transporting large proteins or mRNA from the nucleus to the cytoplasm through the nuclear pore. To understand how CRM1 impacts transport, it is critical to understand the CRM1 molecular structure.

Oct 23, 2024 · In this study, we investigated the subcellular localization and leukemogenic potential of two rare NPM1-fusion proteins, NPM1::MLF1 and NPM1::CCDC28A. NPM1::MLF1 is present in both the nucleus...

Mutations in NPM1, also known as nucleophosmin-1, B23, NO38, or numatrin, are seen in approximately one-third of patients with acute myeloid leukaemia (AML). A plethora of treatment strategies have been studied to determine the best possible approach to curing NPM1 …

Oct 8, 2020 · NPM1 mutations represent the most common genetic lesion in adult acute myeloid leukemia (AML; about one third of cases), and they act deterministically to cause the aberrant cytoplasmic delocalization of NPM1 mutants.