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Carmen-Mariana AANEI

Centre Hospitalier Universitaire de Saint-Etienne, Saint-Etienne, France

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Born: 1900

Interests: mesenchymal stromal cells, myelodysplastic syndromes, focal adhesion proteins

Details:
The studies that I have conducted are related to understanding the place of stromal microenvironment in myelodysplastic syndromes (MDS) pathophysiology which mediates the direct contact with haematopoietic precursor cells (HPCs).
The aims of my PhD thesis were to evaluate the putative growth deficiencies of mesenchymal stromal cells (MSC) from MDS individuals compared with normal controls, to explore their adhesion profile, and further, to assess the molecular substrates involved in the focal adherences that they form, and finally, to perform correlations with their growth dysfunctions and with haematopoietic compartment abnormalities.
To this end, I developed a novel selection protocol in order to obtain a standards-compliant MSC preparation using their different expression for the specific markers STRO-1 and CD73.
Thereafter, I evaluated their adhesion phenotype and the growth patterns of these MSC selected fractions from MDS patients vs. normal controls. Functional assays revealed that the MSCs from MDS are intrinsically pathological, showing a continuous decline of proliferation and a reduced clonogenic capacity during 14 days of culture and in the absence of signals from hematopoietic cells. The MSC growth defects were significantly correlated with decreases in CD44 adhesion molecules and CD49e (α5-integrin). Furthermore, the clonogenic potential of HPC is controlled by adhesion mechanisms dependent on stroma, and α5-integrin might be one of the molecules involved in this process.
Finally, I conducted immunofluorescence experiments to assess two focal adhesion proteins paxillin, and pFAK [Y397], and two regulatory proteins, HSP90αβ, and p130CAS in terms of reactivity, intensity and cellular localization. Immunofluorescence microscopy allowed the identification of qualitative and quantitative differences, and subcellular localization analysis revealed that, in pathological MSCs, paxillin, pFAK, and HSP90αβ form nuclear, molecular complexes. An increased
expression of paxillin, pFAK [Y397], and HSP90αβ, in addition to, their stronger nuclear colocalization, correlated with a consistent proliferative advantage in MSCs from Refractory Anaemia with Excess Blasts (RAEB) and has been shown to have a negative impact on clonogenic capacity of HPCs.
These results open interesting opportunities, e.g. signalling via FA proteins could be implicated in HPC-to-MSC interactions, and, considering that FAK is one of HSP90αβ-client proteins, enhance the utility of HSP90αβ inhibition as a target for adjuvant myelodysplasia therapy.

The results of this study have disseminated in two highly relevant publications, in the field:

 Experimental Cell Research (Carmen Mariana Aanei, Florin Zugun Eloae, Pascale Flandrin, Emmanuelle Tavernier, Eugen Carasevici, Denis Guyotat, Lydia Campos, Focal adhesion protein abnormalities in myelodysplastic mesenchymal stromal cells, Experimental Cell Research 3 1 7 (2 0 1 1); 2 6 1 6 - 2 6 2 9 [PubMed : 21871449]),

 and Stem Cells and Development (Carmen Mariana Aanei, Pascale Flandrin, Florin Zugun Eloae, Eugen Carasevici, Denis Guyotat, Eric Wattel, Lydia Campos, Intrinsic growth deficiencies of mesenchymal stromal cells (MSCs) in myelodysplastic syndromes (MDS), Stem Cells and Development (2012); 21(10):1604-15 [PubMed: 21933023 ]). This article has designated among the top five High Impact Articles from Stem Cells and Development review (July issue).

In adittion, these papers have already cited in a recent review on stromal anomalies in MDS (Raaijmakers, Int J Hematol 2012) and by two articles, one about the cytogenetic modifications of mesenchymal cells selected from MDS patients (Santamaria, Haematologica 2012)and second relevant for the utility of MSC in biotechnologies(Susanta K. Hui, PLoS ONE 2012).

Likewise, the results have communicated in several prestigious scientific meetings. The last one was AACR Annual Meeting 2012, where the American Association for Cancer Research Committee has designated my abstract "Adhesion-mediated dysfunctions in myelodysplastic syndromes microenvironment" as a Highly Rated Paper (abstract scored in the top 2.5% of abstracts presented in the poster sessions).

Selected publications:
• Emmanuelle Tavernier, Carmen Aanei, Françoise Solly, Pascale Flandrin-Gresta , Lydia Campos , Denis Guyotat . CXCR4: a new therapeutic target of the leukaemic cell?. Bulletin du cancer, 2014.
• Carmen Mariana Aanei, Pascale Flandrin, Florin Zugun Eloae, Eugen Carasevici, Denis Guyotat, Eric Wattel, Lydia Campos. Intrinsic growth deficiencies of mesenchymal stromal cells (MSCs) in myelodysplastic syndromes (MDS). Stem Cells and Development, 21(10), pp. 1604-15, 2012.
• Lydia Campos, Nathalie Nadal, Pascale Flandrin-Gresta, Christian Vasselon, Carmen Aanei, Claire Berger, and Jean Louis Stephan. Congenital Acute Leukemia with Initial Indolent Presentation--A Case Report. Cytometry B Clin Cytom, 80(2), pp. 130-3, 2011.
• Carmen Mariana Aanei, Florin Zugun Eloae, Pascale Flandrin, Emmanuelle Tavernier, Eugen Carasevici, Denis Guyotat, Lydia Campos. Focal adhesion protein abnormalities in myelodysplastic mesenchymal stromal cells. Experimental Cell Research, 3 1 7, pp. 2616-2629 , 2011.
• L. Campos, F. Solly, C. Aanei, P. Flandrin, D. Guyotat. HSP90 is overexpressed in high-risk myelodysplastic syndromes and associated with higher expression and activation of FAK. Leukemia Research, 33, p. S45, 2009.

Publications from the ISI database, indexed between 2002-2011, produced in Romania:
• Cianga, P; Cianga, C; Zlei, M; Aanei, C, HLA-B27 flow cytometric labeling patterns may suggest potential cross-reactivities. TISSUE ANTIGENS, 71 (4), pp. P291-, 2008.
• Dascalescu, A; Zlei, M; Grigore, G; Danaila, C; Aanei, C; Burcoveanu, C; Carasevici, E; Hanganu-Turtureanu, E, CYTOKINE RECEPTORS EXPRESSION ON ACUTE MYELOID LEUKEMIA CELLS. HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 94, pp. 1383-, 2009.
• Solly, F; Flandrin-Gresta, P; Aanei, C; Cornillon, J; Tavernier, E; Guyotat, D; Campos, L, High levels of HSP90 in myelodysplastic syndromes are associated with increased expression of signal transducers AKT and FAK, and disease progression. BULLETIN DU CANCER, 97, pp. S60-S61, 2010.
• Solly, F; Flandrin-Gresta, P; Aanei, C; Cornillon, J; Tavernier, E; Guyotat, D; Campos, L, High Levels of Heat Shock Proteins 90 and 27 in CD34-Positive Cells from Myelodysplastic Syndromes (MDS) Are Associated with Higher Expression and Activation of Focal Adhesion Kinase (FAK) and with Disease Progression. BLOOD, 114 (22), p. 122, 2009.
• Campos, L; Aanei, C; Eloae, FZ; Flandrin, P; Solly, F; Guyotat, D; Carasevici, E, MORPHOTYPES AND PHENOTYPES IN PRIMARY CULTURES BONE MARROW MESENCHYMAL CELL FROM HEALTHY DONORS AND MYELODYSPLASTIC PATIENTS. HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 95, pp. 1699-, 2010.
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