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We are analyzing https://link.springer.com/article/10.1186/s13045-016-0235-8.

Title:
GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways | Journal of Hematology & Oncology
Description:
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.
Website Age:
28 years and 1 months (reg. 1997-05-29).

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Keywords {🔍}

mice, mds, pubmed, genes, article, google, scholar, cells, pathways, hrmds, gene, aml, cas, post, expression, additional, table, file, analysis, dysregulated, fig, cell, spleen, central, myelodysplastic, patients, leukemia, disease, transgenic, models, performed, study, model, fvbn, upregulated, myeloid, sca, data, gep, dna, pathway, syndromes, blood, metabolism, downregulated, expressed, compared, acute, syndrome, signaling,

Topics {✒}

quantitative real-time rt-pcr neutralizing anti-igf-1r antibody hypoxia-inducible factor-1alpha expression laure sarda-mantel autocrine igf-1/igf-1r signaling low-/intermediate-1-risk myelodysplastic syndromes pgc-1alpha-responsive genes involved de la grange immature cells lin−sca1+ckit+ article download pdf full size image including dna replication/damage/repair gene expression profile treatment-related myelodysplastic syndrome cbfb-myh11 hypomethylation signature muf1/leucine-rich repeat low-risk myelodysplastic syndromes cell cycle/checkpoints/dna repair rbc transfusion-dependent patients constitutive pi3k/akt activation cell cycle/dna damage-repair modulates cell-cell adhesion anti-sca1+ antibodies coupled hypoxia-inducible factor-1a age-related epigenetic drift anti-cd34+ antibodies coupled immunocompromised rag1-deficient mice hr-mds mice resulting therapy-related myelodysplastic syndromes dna-binding regulatory factor hr-mds mice produced universitĂ© paris diderot hr-mds transgenic mice mitogen-activated protein kinase quantitative reverse transcription-pcr 99tc-annexin spect imaging hr-mds mice compared gene expression profiles hr-mds mouse model animal experiments paris-nord fondation de france rose ann padua single transgenic mice single-transgenic mice mras-bcl2 transgenic mice myelodysplastic syndrome cells mod-list tomographic acquisition treating myelodysplastic syndrome fabien guidez nras/bcl-2 mouse model

Questions {❓}

  • Reactive oxygen species, DNA damage, and error-prone repair: a model for genomic instability with progression in myeloid leukemia?
  • Universal genetic testing for inherited susceptibility in children and adults with myelodysplastic syndrome and acute myeloid leukemia: are we there yet?

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         headline:GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways
         description: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. 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. 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. 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.
         datePublished:2016-01-27T00:00:00Z
         dateModified:2016-01-27T00:00:00Z
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            Myelodysplastic syndrome
            Mice models
            Gene expression profile
            MDS
            Oncology
            Hematology
            Cancer Research
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ScholarlyArticle:
      headline:GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways
      description: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. 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. 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. 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.
      datePublished:2016-01-27T00:00:00Z
      dateModified:2016-01-27T00:00:00Z
      pageStart:1
      pageEnd:20
      license:http://creativecommons.org/publicdomain/zero/1.0/
      sameAs:https://doi.org/10.1186/s13045-016-0235-8
      keywords:
         Myelodysplastic syndrome
         Mice models
         Gene expression profile
         MDS
         Oncology
         Hematology
         Cancer Research
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