Related Experiment Video

Updated: Nov 21, 2025

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

9.3K

NSC348884 cytotoxicity is not mediated by inhibition of nucleophosmin oligomerization

Markéta Šašinková1, Petr Heřman2, Aleš Holoubek1

  • 1Department of Proteomics, Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20, Prague 2, Czech Republic.

Scientific Reports
|January 14, 2021
PubMed

Insights

The drug NSC348884 does not inhibit nucleophosmin (NPM) oligomerization in acute myeloid leukemia (AML) cells. Instead, its cytotoxicity stems from altered cell adhesion signaling, requiring a reevaluation of its mechanism.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Mutations in Nucleophosmin (NPM) lead to its cytoplasmic export in acute myeloid leukemia (AML).
  • Wild-type NPM heterooligomerization with mutant NPM causes NPM mislocalization and functional impairment.
  • Dissociating NPM heterooligomers is a potential strategy to restore wild-type NPM function.

Purpose of the Study:

  • To investigate the effect of NSC348884, a putative NPM oligomerization inhibitor, on NPM heterooligomers.
  • To determine the mechanism of NSC348884 cytotoxicity in AML.

Main Methods:

  • Fluorescence lifetime imaging with Förster resonance energy transfer (FRET).
  • Immunoprecipitation and electrophoretic methods.
  • Studies on leukemia-derived cell lines, primary AML cells, and transfected cells.

Main Results:

  • NSC348884 did not inhibit NPM oligomerization in vitro or in vivo.
  • Cytotoxicity of NSC348884 was linked to modifications in cell adhesion signaling.
  • The proposed mechanism of NPM oligomer inhibition by NSC348884 was not supported.

Conclusions:

  • NSC348884 does not function as an inhibitor of NPM oligomerization.
  • The cytotoxic effects of NSC348884 are associated with altered cell adhesion signaling.
  • The therapeutic mechanism of NSC348884 in AML requires reassessment.

More Related Videos

An Automated Method to Perform The In Vitro Micronucleus Assay using Multispectral Imaging Flow Cytometry12:56

An Automated Method to Perform The In Vitro Micronucleus Assay using Multispectral Imaging Flow Cytometry

Published on: May 13, 2019

22.9K
Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

13.5K

Related Concept Videos

Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
6.1K
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.2K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.3K
Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
7.9K