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Master Thesis

Analyse transcriptomique des cellules stromales mésenchymateuses au cours du traitement du Myélome Multiple

Abstract : Multiple myeloma (MM) is a B-cell malignancy characterized by clonal expansion of malignant plasma cells (PC) within the bone marrow (BM). MM patients often experience multiple relapses due to the presence of chemo-resistant residual MM clones and there is a critical need to understand the mechanisms that regulate MM chemo-resistance and relapse. The interactions between BM cells and malignant PCs play an essential role In MM growth and survival. Mesenchymal stromal cells (MSC) are multipotent BM stromal cells, able to differentiate into osteoblasts and adipocytes that support malignant PC growth through released factors. A better understanding of the role played by these cells in MM drug resistance and relapse is now required. To address this question, we performed a transcriptomic analysis of MSC isolated from healthy donors (HD), and MM patients at different stages of the disease including diagnosis, relapse and after a 2 years remission period. Our results reveal important differences in gene expression between HD and MM MSC. Surprisingly, the transcriptomic profile of MSC was very similar across the different MM stages: relapse or remission. These data reveal that the alteration in MSC gene expression associated with MM development can persist even in the absence of clinical sign of the disease. This suggests that a deep imprinting of MSC cellular program occurs by the contact with MM PCs. This program could be responsible for myeloma relapse even after a long period of time.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-02497330
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Léa Lemaitre. Analyse transcriptomique des cellules stromales mésenchymateuses au cours du traitement du Myélome Multiple. Sciences du Vivant [q-bio]. 2019. ⟨dumas-02497330⟩

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