Study of chronic lymphocytic exosomes and their impact on leukemogenesis

Project Details


Chronic lymphocytic leukemia (CLL) is the most frequent hematologic malignancy in adults characterized by the accumulation of mature Blymphocytes in the blood and lymphoid organs, and remains an incurable disorder. Exosomes are small vesicles released by all cell types in theextracellular space and represent a new component of intercellular communication. Cancer-derived exosomes stimulate tumor progression by influencing the micro environment, favoring angiogenesis and the growth and migration of cancer cells. Exosomes can be captured by target cells,deliver their protein and nucleic acid content in order to modulate cellular functions of these target cells. After having shown the pro-leukemogeniceffect of CLL-derived exosomes on stromal cells (Paggetti et al., manuscript in revision), we would like to study in more detail their content and confirm their role in the development of CLL in vivo.The first part of this project consists in the characterization of CLL-derived
exosomes to identify new oncogenic molecules as well as potential biomarkers. A detailed characterization of purified CLL-derived exosomeswill be performed with high-throughput methods (mass spectrometry,microarrays, and RNA sequencing). The role of candidates will then be validated by silencing experiments.In parallel, we plan to use the Eμ-TCL1 mouse model, which is developing a spontaneous CLL, and to cross them with the Rab27-deficientRab27aash/ashRab27b-/- mice, a second murine model unable to secrete exosomes. This new murine model will allow us to study the role of exosomes in the development of CLL in vivo.In conclusion, this study will lead to a better characterization of CLL-derived exosomes and to a better understanding of the tumorigenic mechanisms linked to exosomes.
Effective start/end date1/01/1631/12/17


  • FNRS - Fonds National de la Recherche Scientifique: €224,000.00


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