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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