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In vivo study of the role of CCAAT Enhancer binding protein alpha (CEBPA)gene hipoexpression in the leukemogenesis induced by the CALM/AF10 hybrid protein.

Grant number: 11/17111-4
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2011
Effective date (End): August 31, 2015
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Eduardo Magalhães Rego
Grantee:Ana Paula Alencar de Lima Lange
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


The rare but recurrent chromosomal translocation t(10; 11)(p13; q14), which results in the CALM/AF10 fusion gene, is found in patients with Acute Lymphoid Leukemia (ALL) and Acute Myeloid Leukemia (AML) or Acute Leukemia of Ambiguous Lineage. Leukemias harboring CALM/AF10 oncogene are associated with poor response to treatment and shorter disease-free survival and overall survival. These leukemias present increased expression of HOXAI genes. Recipient mice transplanted with retrovirus-transfected bone marrow cells expressing CALM/AF10 gene may develop leukemia, whose latency is of 9-14 weeks. In contrast, transgenic mice expressing CALM/AF10 under LCK promoter do not present hematopoietic alterations. Gene expression analysis using the Affymetrix platform showed a significantly lower expression of the gene encoding for the transcription factor CCAAT Enhancer binding protein alpha (CEBPA) in CALM/AF10 patients in comparison to different subtypes of leukemia and health donors. Therefore, the main objective of this project is to analyze the role of hipoexpressed CEBPA gene in the leukemogenesis induced by CALM/AF10 fusion gene using a genetically modified animal model.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LANGE, ANA P.; LIMA, ANA S.; LUCENA-ARAUJO, ANTONIO R.; JACOMO, RAFAEL H.; MELO, RAUL A.; BITTENCOURT, ROSANE I.; PASQUINI, RICARDO; PAGNANO, KATIA; FAGUNDES, EVANDRO M.; CHAUFFAILLE, MARIA L.; et al. The experience of the International Consortium on Acute Promyelocytic Leukemia in monitoring minimal residual disease in acute promyelocytic leukaemia. British Journal of Haematology, v. 180, n. 6, p. 915-918, . (11/17111-4, 13/08135-2)
DE ALMEIDA, LUCIANA YAMAMOTO; PEREIRA-MARTINS, DIEGO A.; WEINHAEUSER, ISABEL; ORTIZ, CESAR; CANDIDO, LARISSA A.; LANGE, ANA PAULA; DE ABREU, NAYARA F.; MENDONZA, SILVIA E. S.; DE DEUS WAGATSUMA, VIRGINIA M.; DO NASCIMENTO, MARIANE C.; et al. The Combination of Gefitinib With ATRA and ATO Induces Myeloid Differentiation in Acute Promyelocytic Leukemia Resistant Cells. FRONTIERS IN ONCOLOGY, v. 11, . (17/00775-3, 16/17521-1, 10/16966-3, 15/09228-0, 17/23117-1, 13/08135-2, 13/11817-8, 11/18313-0, 11/17111-4, 16/02713-2, 17/08430-5)
LANGE, A. P.; ALMEIDA, L. Y.; ARAUJO SILVA, C. L.; SCHEUCHER, P. S.; CHAHUD, F.; KRAUSE, A.; BOHLANDER, S. K.; REGO, E. M.. CCAAT/enhancer-binding protein alpha (CEBPA) gene haploinsufficiency does not alter hematopoiesis or induce leukemia in Lck-CALM/AF10 transgenic mice. Brazilian Journal of Medical and Biological Research, v. 52, n. 6, . (16/02713-2, 13/08135-2, 11/17111-4)

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