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Study of therapeutic targets in hematologic malignancies


Currently it is clear the participation of different signaling pathways involved in both the development and the maintenance of hematologic malignancies. The constitutive activation of PI3K/Akt/mTOR signaling pathway is well described in acute lymphoblastic leukemia T cells (T-ALL), and recently it was found that the activity of PI3K cooperates with the development of Burkitt's lymphoma. Thus, the role of PI3K/Akt/mTOR in cell growth and survival, two important characteristics of leukemogenesis, has become a potential pharmacological target in different types of hematological malignancies. One goal of this project is to study the therapeutic potential of a drug highly selective for inhibition of PI3K, NVP-BKM120, developed by Novartis, in cell lines of T-ALL and Burkitt's lymphoma. In addition to the constant investment in new specific drugs to destroy the cancer cell, the bone marrow microenvironment has emerged as an important therapeutic target. It is clear the participation of bone marrow milieu on survival, immune surveillance and resistance to conventional therapy of cancer cell. In this context, several evidences suggest the involvement of mesenchymal stromal cells (MSC), which are part of the bone microenvironment in the pathophysiology of myelodysplastic syndromes (MDS). Recently, it was reported an increase in expression of IL-32 in MSC of MDS patients and their contribution to the pathophysiology of this disease. Thus, it is also objective of this study was to characterize the functional relevance of IL32, a possible therapeutic target in MSC of MDS patients. (AU)

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