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Updated: Apr 2, 2026
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Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
Published on: September 1, 2019
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Examining the Effects of the RUNX1 p.Leu43Ser Variant on FPD/AML Phenotypes Using a CRISPR/Cas9-Generated Knock-In
Ana Marin-Quilez1,2, Ignacio García-Tuñón1,3, Rocío Benito1
1Cancer Research Center-CSIC, Instituto de Investigación Biomédica de Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain.
Biomolecules
|May 28, 2025
Summary
Germline RUNX1 variants can cause Familial Platelet Disorder with Myeloid Leukemia Predisposition (FPD/AML). This study found that the RUNX1 L43S variant, particularly in homozygous form, may contribute to aberrant cell development in mice.
Area of Science:
- Hematology
- Genetics
- Oncology
Background:
- Germline heterozygous variants in the RUNX1 gene are associated with Familial Platelet Disorder with Myeloid Leukemia Predisposition (FPD/AML).
- Understanding the role of specific variants in disease pathogenesis requires robust cellular and animal models.
Purpose of the Study:
- To investigate the in vivo effects of the RUNX1 L43S variant, focusing on its potential contribution to myeloid leukemia predisposition.
- To characterize the hematological and molecular consequences of RUNX1 L43S homozygosity and heterozygosity in a mouse model.
Main Methods:
- Generation of RUNX1 L43S mutant mice (homozygous and heterozygous) using CRISPR/Cas9.
- Analysis of peripheral blood, bone marrow, and spleen using flow cytometry and histopathology.
- RNA sequencing (RNA-seq) of bone marrow to identify deregulated genes.
Main Results:
- An aberrant myeloid Mac1+Sca1+ckit- cell population and bone marrow hypercellularity were observed in RUNX1 L43S homozygous and heterozygous mice, particularly after irradiation.
- Homozygous mice exhibited spleen pathology, including white/red pulp destruction and apoptosis.
- RNA-seq revealed significant deregulation of genes involved in apoptosis and DNA repair in mice with the aberrant cell population.
Conclusions:
- The homozygous RUNX1 L43S variant may contribute to the pathogenesis of aberrant myeloid cells.
- This mouse model provides insights into the mechanisms underlying FPD/AML associated with RUNX1 variants.
