Quiescence exit of BCR-ABL leukemic stem cells under tyrosine kinase inhibitors : Central role of Rho family GTPases 4CS Laboratory - Poitiers

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BCR-ABL is a fusion oncoprotein expressed by a fusion oncogene found in the Philadelphia chromosome, responsible for the development of Chronic Myeloide Leukemia. Indeed, this abnormal protein contains a Tyrosine kinase activity (TK) domain which is constitutively active causing an intense activation of the Rac pathway, and a DH/PH domain which activate the RhoA pathway.

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However, when treated with tyrosine kinase inhibitors (TKI) and a calcic canals inhibitor called SKF-96365, ROCK1 mediated pathway and Rac pathway are inhibited but not RhoA. So during this internship, I’m going to study the reinstatement of the normal ROCK1 and Rac pathways in the presence of TKI and a calcic canals inhibitors called SKF-96365 in quiescent leukemic cells. 

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As a matter of facts, those inhibited pathways are fully reactivated only when SKF-96365, Epidermal Growth Factor (EGF) and TKI are added in the medium. 

For the purpose of this internship, the different actors activated by RhoA and ROCK1 will be analyzed in various conditions such as the presence of both TKI and SKF-96365 in the medium, or TKI only, or none of them