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Investigation of molecular alterations in myeloid neoplasms.

Grant number: 12/09982-8
Support Opportunities:Regular Research Grants
Start date: October 01, 2012
End date: March 31, 2015
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Fabíola Traina
Grantee:Fabíola Traina
Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The World Health Organization distinguishes four groups of myeloid neoplasm: myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), MPN/MDS and acute myeloid leukemia (AML). MPN and MDS can evolve into AML, a group of neoplasm characterized by clonal myeloid blast proliferation and high mortality. The concept of drugs that act selectively on the neoplastic cells is attractive and there are many potential targets to be studied. Recently, a large number of new data has shown that the presence of cytogenetic abnormalities can have prognostic value and therapeutic implications in myeloid neoplasm. In addition, epigenetic changes can significantly impact in the chromatin structure and in the transcriptional process. Proteins known to be involved in other types of cancer or in important signaling pathways can also participate in the pathophysiology of the myeloid neoplasm. New studies investigating the clinical and biological impact of each molecular alteration are important for the better understanding of the biology of these diseases, the identification of prognostic markers, the prediction of response to drugs and the finding of new therapeutic targets. Our main goal is to study the role of specific proteins, through gene silencing, in the neoplastic process and in the drug response in myeloid neoplasm, in particular, the study of TET2, DNMT3A and IRS proteins. Concomitantly, we also aim to investigate gene mutations possible involved in myeloid neoplasm and their clinical correlations. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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Scientific publications (4)
(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)
TRAINA, F.; VISCONTE, V.; ELSON, P.; TABARROKI, A.; JANKOWSKA, A. M.; HASROUNI, E.; SUGIMOTO, Y.; SZPURKA, H.; MAKISHIMA, H.; O'KEEFE, C. L.; et al. Impact of molecular mutations on treatment response to DNMT inhibitors in myelodysplasia and related neoplasms. LEUKEMIA, v. 28, n. 1, p. 78-87, . (12/09982-8, 11/20750-9)
MACHADO-NETO, JOAO AGOSTINHO; LAZARINI, MARIANA; FAVARO, PATRICIA; CAMPOS, PAULA DE MELO; SCOPIM-RIBEIRO, RENATA; FRANCHI JUNIOR, GILBERTO CARLOS; NOWILL, ALEXANDRE EDUARDO; MOURA LIMA, PAULO ROBERTO; COSTA, FERNANDO FERREIRA; BENICHOU, SERGE; et al. ANKHD1 silencing inhibits Stathmin 1 activity, cell proliferation and migration of leukemia cells. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v. 1853, n. 3, p. 583-593, . (09/00268-8, 11/51959-0, 11/06840-5, 12/09982-8)
SCOPIM-RIBEIRO, RENATA; MACHADO-NETO, JOAO AGOSTINHO; CAMPOS, PAULA DE MELO; NIEMANN, FERNANDA SOARES; LORAND-METZE, IRENE; COSTA, FERNANDO FERREIRA; OLALLA SAAD, SARA TERESINHA; TRAINA, FABIOLA. Low Ten-eleven-translocation 2 (TET2) transcript level is independent of TET2 mutation in patients with myeloid neoplasms. DIAGNOSTIC PATHOLOGY, v. 11, . (11/51959-0, 12/09982-8, 11/15905-3)
MACHADO-NETO, JOAO AGOSTINHO; CAMPOS, PAULA DE MELO; FAVARO, PATRICIA; LAZARINI, MARIANA; SANTOS DUARTE, ADRIANA DA SILVA; LORAND-METZE, IRENE; COSTA, FERNANDO FERREIRA; OLALLA SAAD, SARA TERESINHA; TRAINA, FABIOLA. Stathmin 1 inhibition amplifies ruxolitinib-induced apoptosis in JAK2(V617F) cells. ONCOTARGET, v. 6, n. 30, p. 29573-29584, . (11/51959-0, 11/06840-5, 12/09982-8, 14/23092-0)