Suppression of malignant rhabdoid tumors through Chb-M'-mediated RUNX1 inhibition

Pediatr Blood Cancer. 2021 Feb;68(2):e28789. doi: 10.1002/pbc.28789. Epub 2020 Nov 12.

Abstract

Malignant rhabdoid tumor (MRT) is a rare and highly aggressive pediatric malignancy primarily affecting infants and young children. Intensive multimodal therapies currently given to MRT patients are not sufficiently potent to control this highly malignant tumor. Therefore, additive or alternative therapy for these patients with a poor prognosis is necessary. We herein demonstrated that the inhibition of runt-related transcription factor 1 (RUNX1) by novel alkylating conjugated pyrrole-imidazole (PI) polyamides, which specifically recognize and bind to RUNX-binding DNA sequences, was highly effective in the treatment of rhabdoid tumor cell lines in vitro as well as in an in vivo mouse model. Therefore, suppression of RUNX1 activity may be a novel strategy for MRT therapy.

Keywords: RUNX1; malignant rhabdoid tumor; p53; polyamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Cell Line, Tumor
  • Chlorambucil / analogs & derivatives
  • Chlorambucil / therapeutic use*
  • Core Binding Factor Alpha 2 Subunit / antagonists & inhibitors*
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Disease Models, Animal
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Rhabdoid Tumor / drug therapy*
  • SMARCB1 Protein / genetics
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Alkylating
  • Core Binding Factor Alpha 2 Subunit
  • RNA, Small Interfering
  • RUNX1 protein, human
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • Chlorambucil