Skip to Main content Skip to Navigation
Journal articles

GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways.

Abstract : 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [87 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01322492
Contributor : Bmc Bmc <>
Submitted on : Friday, May 27, 2016 - 11:26:07 AM
Last modification on : Wednesday, August 19, 2020 - 11:18:08 AM
Long-term archiving on: : Sunday, August 28, 2016 - 10:36:31 AM

Files

13045_2016_Article_235.pdf
Publication funded by an institution

Identifiers

Collections

Citation

Laura Guerenne, Stéphanie Beurlet, Mohamed Said, Petra Gorombei, Carole Le Pogam, et al.. GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways.. Journal of Hematology and Oncology, BioMed Central, 2016, 9 (1), pp.5. ⟨10.1186/s13045-016-0235-8⟩. ⟨inserm-01322492⟩

Share

Metrics

Record views

297

Files downloads

753