Advanced search
Start date
Betweenand

Analysis of the gene expression profile of acute myeloid leukemia subtypes with C/EBPA genetic abnormalities

Grant number: 11/11822-6
Support type:Scholarships abroad - Research
Effective date (Start): November 01, 2011
Effective date (End): October 31, 2012
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Lorena Lôbo de Figueiredo Pontes
Grantee:Lorena Lôbo de Figueiredo Pontes
Host: Daniel Goeffrey Tenen
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Local de pesquisa : Harvard University, Boston, United States  

Abstract

Knowledge of the mechanisms underlying the normal development of blood cells will lead to new understanding of the pathogenesis of acute leukemias. Previous studies have demonstrated the role of the transcription factor abnormalities in acute myeloid leukemia (AML) in humans although this knowledge needs to be better translated into prognostic and therapeutic information. The major hypotheses underlying leukemogenesis in AML are: (1) AML is characterized by a block in hematopoietic cell differentiation; (2) hematopoietic cell differentiation is largely determined by lineage specific transcription factors; (3) abnormalities in these transcription factors are likely to play a major role in AML and will result in distinct patterns of gene expression; (4) characterization of these gene expression clusters will lead to new classifications of AML and identification of new target genes and pathways directed to new strategies for treatment. Studies from Prof. Daniel G. Tenen's laboratory (Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA) have led to the identification of the transcription factor CCAAT Enhancer Binding Protein alpha (C/EBPA), encoded in humans by the CEBPA gene, as being absolutely critical for differentiation of normal myeloid blasts. It has been demonstrated that specific abnormalities in C/EBPA (mutations, decreased expression, and abnormal cellular localization) are found in specific subtypes of AML and contribute to the leukemic phenotype. In addition, recent studies from Prof. Ruud Delwel (Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands) have shown distinct gene expression clusters in patients with mutations in C/EBPA, as well as new target genes. Based on these data, this research project intends to establish if these gene expression clusters can be utilized for new prognostic strategies, as well as to understand more about the mechanism of how mutations of C/EBPA lead to a block in differentiation. The results of such investigation will be useful to eventually develop more specific, less toxic therapies for leukemia and other cancers. (AU)

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)
DI RUSCIO, ANNALISA; EBRALIDZE, ALEXANDER K.; BENOUKRAF, TOUATI; AMABILE, GIOVANNI; GOFF, LOYAL A.; TERRAGNI, JOLYON; FIGUEROA, MARIA EUGENIA; PONTES, LORENA LOBO DE FIGUEIREDO; ALBERICH-JORDA, MERITXELL; ZHANG, PU; WU, MENGCHU; D'ALO, FRANCESCO; MELNICK, ARI; LEONE, GIUSEPPE; EBRALIDZE, KONSTANTIN K.; PRADHAN, SRIHARSA; RINN, JOHN L.; TENEN, DANIEL G. DNMT1-interacting RNAs block gene-specific DNA methylation. Nature, v. 503, n. 7476, p. 371+, NOV 21 2013. Web of Science Citations: 249.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.