test_moissonnage_selune
type: Agent

Study of marrow microenvironment and focal adherences in myelodysplastic syndromes and leukemias
type: Dataset
contact point: Organization
  fn: CCSD
keyword: myelodisplastic-syndromes
keyword: proteines-dadherence-focale
keyword: sdvmheplife-sciences-q-biohuman-health-and-pathology
keyword: growth-patterns
keyword: mesenchymal-stroma-cells
keyword: focal-adhesion-proteins
keyword: modeles-de-croissance
keyword: theses
keyword: paxillin
keyword: cellules-stromales-mesenchymateuses
keyword: infoeu-reposemanticsdoctoralthesis
keyword: paxilline
keyword: refractory-aneamia-with-excess-blasts
keyword: syndromes-myelodisplasiques
landing page: https://theses.hal.science/tel-00955168
description: Myelodysplastic syndromes (MDS) are regarded as clonal disorders of haematopoietic stem cells (HSC). Recent evidence demonstrates that stromal microenvironment, in addition to HSC defects, plays a particular role via its direct contact with haematopoietic precursor cells (HPC). This thesis aims at evaluating the putative growth deficiencies of mesenchymal stromal cells (MSC) from MDS individuals compared with normal controls, exploring their adhesion profile, assessing the adhesion process-involved molecular substrates, and establishing correlations with their growth patterns and HPC dysfunctions. Functional assays revealed that MSC from MDS are intrinsically pathological, show a continuous decline of proliferation over a 14-day culture and a reduced clonogenic capacity in the absence of signals from HPC. MSC growth defects significantly correlate with decreased CD44 and CD49e expression. Moreover, stroma-dependent adhesion mechanisms control HPC clonogenic potential and CD49e might be one of the molecules involved in this process. Qualitative and quantitative abnormalities of focal adhesion (FA) proteins paxillin and pFAK [Y397] and of two regulatory proteins, HSP90αβ and p130CAS were identified via immunofluorescence analysis. Paxillin, pFAK [Y397] and HSP90αβ increased expression, besides its stronger nuclear colocalization in MSC from RAEB correlates with a consistent proliferative advantage and has a negative impact on HPC clonogenic capacity. These results open interesting opportunities, e.g. HPC-to-MSC interactions involve FA proteins signalling, and, as FAK is an HSP90αβ-client protein, it may enhance the utility of HSP90αβ inhibitors as adjuvant therapy in MDS
identifier: NNT: 2012STET001T
issued: 2026-05-06T03:52:39.569552
language: en
modified: 2026-05-06T03:52:39.569556

Study of marrow microenvironment and focal adherences in myelodysplastic syndromes and leukemias
type: Distribution
access URL: https://theses.hal.science/tel-00955168
format: HTML
issued: 2026-05-06T03:52:39.621761
modified: 2026-05-06T03:52:39.552010