Related Experiment Video

Updated: Aug 8, 2026

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
09:16

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells

Published on: September 1, 2019

Expression of RUNX1::RUNX1T1 deregulates the proteome, induces C/EBPβ suppression, and blocks myeloid differentiation

Aleksandra Azevedo1, Adam Leckenby1, Rachael Nicholson1

  • 1Division of Cancer and Genetics, Department of Haematology, School of Medicine, Cardiff University, Cardiff, United Kingdom.

Blood Neoplasia
|August 7, 2026
PubMed

Insights

RUNX1::RUNX1T1 fusion protein in acute myeloid leukemia (AML) disrupts myeloid development by altering the proteome, specifically downregulating CCAAT/enhancer-binding protein beta (C/EBPβ). This impacts myeloid cell proliferation and differentiation, contributing to leukemia pathogenesis.

Area of Science:

  • Hematology
  • Molecular Biology
  • Cancer Research

Background:

  • Acute myeloid leukemia (AML) is often associated with the RUNX1::RUNX1T1 fusion gene, which impairs myeloid development.
  • The proteome alterations in human hematopoietic stem and progenitor cells (HSPCs) driven by RUNX1::RUNX1T1 are not well understood.

Purpose of the Study:

  • To investigate the proteomic changes in human HSPCs expressing RUNX1::RUNX1T1.
  • To elucidate the role of CCAAT/enhancer-binding protein beta (C/EBPβ) in RUNX1::RUNX1T1-mediated myeloid deregulation and leukemia development.

Main Methods:

  • Mass spectrometry was employed to analyze the proteome of human HSPCs with RUNX1::RUNX1T1 expression.
  • Functional studies involved ectopic expression and short hairpin RNA (shRNA)-mediated knockdown of C/EBPβ in human myeloid cells.

Main Results:

  • RUNX1::RUNX1T1 expression in HSPCs led to differential expression of 257 proteins, including significant downregulation of C/EBPβ.
  • Ectopic C/EBPβ enhanced myeloid cell proliferation, while C/EBPβ knockdown inhibited normal myeloid growth but promoted growth in RUNX1::RUNX1T1-expressing cells.
  • C/EBPβ influenced myeloid lineage commitment, with its overexpression favoring monocyte development and reduced expression favoring granulocyte differentiation.

Conclusions:

  • RUNX1::RUNX1T1 significantly alters the HSPC proteome, with C/EBPβ downregulation being a key event.
  • C/EBPβ plays a critical role in regulating myeloid cell proliferation and differentiation, and its dysregulation by RUNX1::RUNX1T1 contributes to AML pathogenesis.
  • C/EBPβ acts as a potential lineage discriminator in myeloid development, offering insights into leukemia mechanisms.

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