Análise do papel do C/EBP na leucogênese induzida pela proteína híbrida CALM/AF10

• Processo: 08/51503-4
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Data de Início da vigência: 01 de abril de 2008
• Data de Término da vigência: 31 de maio de 2010
• Área de conhecimento: Ciências Biológicas - Genética - Genética Animal
• Pesquisador responsável: Eduardo Magalhães Rego
• Beneficiário: Alexandre Krause
• Instituição Sede: Hemocentro de Ribeirão Preto. Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Secretaria da Saúde (São Paulo - Estado). Ribeirão Preto , SP, Brasil
• Vinculado ao auxílio: 98/14247-6 - Center for Research on Cell-Based Therapy, AP.CEPID
• Assunto(s): Cultura de células Biologia molecular Hematologia
• Palavra(s)-Chave do Pesquisador: Biologia Molecular | Cultura De Celulas | Hematologia | Leucemias | Modelo Transgenico Murino | Patologia Clinica Veterinaria

Resumo

The rare but recurring chomosomal translocation t(10;11)(p13;q14), which results in the CALM/AF10 fusion, is found in patients with acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), acute biphenotypic leukemia (ABL) and in malignant lymphoma (ML). CALM/AF10 - positive leukemias have a bad prognosis like leukemias with fusions involving the MLL gene. This leukemia presents an over expression pattern of the HOXA genes, similar to the MLL - associated leukemias. Mice transplanted with murine bone marrow retrovirally expressing CALM/AF10 die with an aggressive leukemia with a latency of 9 to 14 weeks. In contrast, transgenic mice expressing CALM/AF10 under the control of the LCK or IgH promoter do not show a leukemia phenotype. Gene expression analysis using the Affymetrix platform comparing 10 CALM/AF10 patient samples to ten groups of different leukemia subtypes and normal bone marrow showed a down regulation in the expression of the myeloid transcription factor CCAAT enhancer-binding protein alpha (C/EBP) in CALM/AF10 patients in comparison to all other groups. The aim of this project is to analyze the role of C/EBP in the leukemogenesis induced by the CALM/AF10 fusion using two different animal models: the retroviral expression of CALM/AF10 in primary murine bone marrow cells transplanted into wild type and C/EBP mice and the transgenic model by crossing CALM/AF10 knock-in with C/EBP mice. (AU)