Pascale Flandrin

Publications (7)21.08 Total impact

• Article: Focal adhesion protein abnormalities in myelodysplastic mesenchymal stromal cells.

  Carmen Mariana Aanei, Florin Zugun Eloae, Pascale Flandrin-Gresta, Emmanuelle Tavernier, Eugen Carasevici, Denis Guyotat, Lydia Campos
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  ABSTRACT: Direct cell-cell contact between haematopoietic progenitor cells (HPCs) and their cellular microenvironment is essential to maintain 'stemness'. In cancer biology, focal adhesion (FA) proteins are involved in survival signal transduction in a wide variety of human tumours. To define the role of FA proteins in the haematopoietic microenvironment of myelodysplastic syndromes (MDS), CD73-positive mesenchymal stromal cells (MSCs) were immunostained for paxillin, pFAK [Y(397)], and HSP90α/β and p130CAS, and analysed for reactivity, intensity and cellular localisation. Immunofluorescence microscopy allowed us to identify qualitative and quantitative differences, and subcellular localisation analysis revealed that in pathological MSCs, paxillin, pFAK [Y(397)], and HSP90α/β formed nuclear molecular complexes. Increased expression of paxillin, pFAK [Y(397)], and HSP90α/β and enhanced nuclear co-localisation of these proteins correlated with a consistent proliferative advantage in MSCs from patients with refractory anaemia with excess blasts (RAEB) and negatively impacted clonogenicity of HPCs. These results suggest that signalling via FA proteins could be implicated in HPC-MSC interactions. Further, because FAK is an HSP90α/β client protein, these results suggest the utility of HSP90α/β inhibition as a target for adjuvant therapy for myelodysplasia.
  Experimental Cell Research 08/2011; 317(18):2616-29. · 3.58 Impact Factor
• Article: Prognostic value of CXCR4 and FAK expression in acute myelogenous leukemia.

  Emmanuelle Tavernier-Tardy, Jérôme Cornillon, Lydia Campos, Pascale Flandrin, Amélie Duval, Nathalie Nadal, Denis Guyotat
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  ABSTRACT: We analysed, by flow cytometry, the "adhesive" phenotype of acute myelogenous leukemia (AML) cells from 36 patients treated in our institution. In univariate analysis, the main prognostic factor for CR achievement was lower CXCR4 expression (p=0.03). Overall survival (OS) was negatively influenced by higher CXC chemokine receptor 4 (CXCR4) (p=0.01), very late antigen-4 (VLA-4) (p=0.01), and focal adhesion kinase (FAK) expression (p=0.04). Combination of these markers allowed to distinguish two prognostic groups: patients overexpressing 2 or 3 factors had a significantly shorter OS (p=0.015). CXCR4, VLA-4 and FAK are new phenotypic markers which could be helpful to establish risk-stratified therapeutic strategies.
  Leukemia research 12/2008; 33(6):764-8. · 2.36 Impact Factor
• Article: Significance of heat-shock protein (HSP) 90 expression in acute myeloid leukemia cells.

  Pascale Flandrin, Denis Guyotat, Amélie Duval, Jérôme Cornillon, Emmanuelle Tavernier, Nathalie Nadal, Lydia Campos
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  ABSTRACT: The 90-kDa heat shock protein (HSP90) is implicated in the conformational maturation and stabilization of a variety of client proteins with receptor and signal transduction functions. The objective of this study was to assess its expression in primary acute myeloid leukemia (AML) cells and to evaluate its biological and clinical significance. The in vitro effects of 17-AAG, a selective inhibitor of HSP90, was also evaluated. Cells from 65 patients with newly diagnosed AML were studied. The expression of HSP90 correlated with that of CD34, p170, and bcl-2 proteins but not with white cell counts, FAB or WHO subtype, or cytogenetics. HSP90 levels were also higher in samples exhibiting an autonomous growth in liquid culture or forming spontaneous colonies. A concomitant constitutive activation of the extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/AKT pathways was observed in a majority of samples and was significantly correlated with HSP90 expression. All patients received induction chemotherapy. The percentages of HSP90-, CD34-, bcl-2-, and p170-positive cells were higher in patients who did not attain complete remission. Survival was also shorter in patients with high levels of HSP90. In vitro exposure of leukemic cells to 17-allylamino-demethoxy geldanamycin (17-AAG) resulted in inhibition of growth in liquid and clonogeneic cultures and in apoptosis, at concentrations which in most cases were not toxic for normal CD34-positive or progenitor cells. The concentration inhibiting 50% growth at 72 h in liquid culture correlated with HSP90 expression. Our study suggests that HSP90 is overexpressed in poor-prognosis AML cells and plays a role in cell survival and resistance to chemotherapy. Targeted therapy with 17-AAG represents a promising antileukemic strategy in adult AML.
  Cell Stress and Chaperones 05/2008; 13(3):357-64. · 3.01 Impact Factor
• Article: RUNX1 rearrangements in acute myeloblastic leukemia relapsing after hematopoietic stem cell transplantation.

  Nathalie Nadal, Jean Louis Stephan, Jerome Cornillon, Denis Guyotat, Pascale Flandrin, Lydia Campos
  Cancer Genetics and Cytogenetics 02/2008; 180(2):168-9. · 1.39 Impact Factor
• Article: Successful treatment with imatinib mesylate in a case of chronic myeloproliferative disorder with a t(5;12)(q33;p13.1) without eosinophilia.

  Nathalie Nadal, Pascale Flandrin, Jerome Cornillon, Eric Delabesse, Laurent Mauvieux, Daniela Olaru, Sylvie Morel, Lydia Campos
  Cancer Genetics and Cytogenetics 10/2006; 169(2):174-5. · 1.39 Impact Factor
• Source

  Available from: haematologica.it

  Article: Expression and prognostic significance of heat-shock proteins in myelodysplastic syndromes.

  Amélie Duval, Daniela Olaru, Lydia Campos, Pascale Flandrin, Nathalie Nadal, Denis Guyotat
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  ABSTRACT: Using flow cytometry, we investigated the clinical and hematologic relevance of expression of heat-shock proteins (HSP) HSP27, HSP60, HSP70, HSP90 and HSP110 in bone marrow of 142 patients with newly diagnosed myelodysplastic syndromes, together with that of the membrane differentiation antigen CD34 and the drug-resistance related protein, P170 (Pgp).
  Haematologica 06/2006; 91(5):713-4. · 6.42 Impact Factor
• Article: Expression of heat-shock proteins is associated with major adverse prognostic factors in acute myeloid leukemia.

  Xavier Thomas, Lydia Campos, Christiane Mounier, Jérome Cornillon, Pascale Flandrin, Quoc-Hung Le, Simone Piselli, Denis Guyotat
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  ABSTRACT: To identify prognostic factors alternative or additional to drug-resistance and apoptosis proteins, we studied the impact of the expression of heat-shock proteins (HSPs) in 98 newly diagnosed acute myeloid leukemia (AML). HSP27 was expressed by 39%, HSP60 by 26%, HSP70 by 58%, HSP90 by 41%, and HSP110 by 30% of cases. HSP expressions were correlated with that of differentiation antigens (CD34, CD14, CD15, CD33) and that of drug-resistance (MRP, MRK) and apoptosis (Bcl-2) proteins. HSP90 and HSP110 were correlated with FAB subtype and karyotypic grouping. Complete remission (CR) was obtained in 68 cases (69%). Median disease-free survival (DFS) of the 68 remitters was 18.1 months with a 3-year DFS rate of 41%. CR rates were higher in patients with lower expression of HSPs. Overall survival (OS) was significantly longer in patients with lower expression of HSPs. Cytogenetics, CD34 positive expression, MRK positive expression, and HSP110 positive expression remained as pejorative prognostic factors for OS in the multivariate analysis. When considering patients with intermediate risk cytogenetics, HSP110 and MRP positive expressions and CD33 negative expression were of poor outcome, while HSP27 and HSP60 positive expressions appeared of pejorative prognostic value in patients with unfavorable karyotypes.
  Leukemia Research 10/2005; 29(9):1049-58. · 2.92 Impact Factor