Related Experiment Video
Updated: Mar 26, 2026
Author Spotlight: Analyzing Bone Marrow Microenvironment in Murine Hematological Malignancies
Published on: November 10, 2023
GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel
Laura Guerenne1,2, Stéphanie Beurlet3,4, Mohamed Said5
1Université Paris-Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Unité Mixte de Recherche (UMR-S) 1131, Paris, France. lguerenne@gmail.com.
Background:
In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS) patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease.
Methods:
We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS) and acute myeloid leukemia (AML) post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively.
Results:
Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples.
Conclusions:
These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.
Insights
New mouse models of myelodysplastic syndromes (MDS) reveal novel pathways involved in disease progression. These models validate known pathways and identify new targets for MDS and acute myeloid leukemia (AML) research.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Myelodysplastic syndromes (MDS) pathophysiology remains unclear despite known genetic mutations.
- Limited in vivo models exist for studying MDS development and progression.
Purpose of the Study:
- To develop and validate novel transgenic mouse models for high-risk MDS (HR-MDS) and acute myeloid leukemia (AML) post-MDS.
- To identify dysregulated gene pathways in MDS using these models.
Main Methods:
- Global gene expression profiling and functional pathway analysis in Sca1+ cells from two MDS transgenic mouse models.
- Comparison of gene expression between diseased mice, founder mice, and human MDS patient samples.
Main Results:
- Validated known MDS-associated pathways (DNA replication/repair, cell cycle, apoptosis, immune responses, canonical Wnt).
- Discovered novel dysregulated pathways in MDS, including noncanonical Wnt signaling and energy/lipid metabolism.
- Confirmed dysregulated genes in independent mouse samples and human MDS patient samples.
Conclusions:
- The developed MDS mouse models are valuable preclinical tools.
- These models can be used to target previously identified MDS pathways and explore newly discovered pathways.
More Related Videos
06:39Use of Hematopoietic Stem Cell Transplantation to Assess the Origin of Myelodysplastic Syndrome
Published on: October 3, 2018
09:33Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens
Published on: August 25, 2023
