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IL-4 and TAL1 in T-cell acute lymphoblastic leukemia : studies on the participation of microenvironmental cues and cell-autonomous alterations in leukemogenesis

Cardoso, Bruno António Caetano, 1982-
Fonte: Universidade de Lisboa Publicador: Universidade de Lisboa
Tipo: Tese de Doutorado
Publicado em //2011 Português
Relevância na Pesquisa
56.23%
Tese de doutoramento, Ciências Biomédicas (Ciências Morfológicas), Universidade de Lisboa, Faculdade de Medicina, 2011; Acute lymphoblastic leukemia (ALL) is the most frequent cancer found in children and results from the clonal expansion of transformed lymphoid precursors. Approximately 15% of pediatric ALL patients present with a T-cell phenotype (T-ALL). Despite the recent improvements in the treatment of T-ALL, there are still a high number of relapses and the intensive chemotherapeutic regiments used are associated with long-term severe complications. In order to develop new therapeutic strategies that can further increase efficacy while reducing side effects, one needs to better understand the pathobiology of T-ALL. In particular, it is necessary to understand how microenvironmental and cell-autonomous mechanisms influence the initiation and the progression of leukemia. The present thesis has the preocupation of exploring the mechanisms by which both an extracellular cue (IL-4) and a cell-intrinsic transcription factor (TAL1) may partake in leukemia development and maintenance. Interleukin-4 (IL-4) is a γ-common chain cytokine produced within the bone marrow microenvironment that is known to promote the in vitro proliferation of T-ALL cells. In Chapter 2...