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Analysis of hnRNPK protein in cell lines NB4 and NB4-R2 of acute myeloid leukemia with emphasis in pathogenesis and cell differentiation by all-trans retinoic acid

Grant number: 13/00374-8
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): April 01, 2013
Effective date (End): January 31, 2017
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Andréia Machado Leopoldino
Grantee:Karina Stringhetta Padovani
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The Acute Promyelocytic Leukemia is characterized mainly by chromosomal translocation t(15,17), that ends in fusion of PML (Promyelocytic Leukemic Protein) and RARa (Retinoic Acid Receptor) genes, generating the PML-RARa oncogene. This gene encodes a retinoic acid receptor mutant that contributes to leukemogenesis by interfering in the process of cell differentiation blocking the same at promyelocytic stage. The translocation t (11, 17) (q23, 21) which also ends in acute promyelocytic leukemia, generates the PLZF-RARa oncogene responsible for the resistance to all-trans retinoic acid (ATRA). The ATRA unlike chemotherapeutics that aim eliminated neoplastic cells in antineoplastic therapy is used for inducing the differentiation and maturation of granulocytes in neoplastic promyelocytes. The treatment provides a good prognosis, but is unfavorable when the leukemic cell is resistant to ATRA. The aim of this project is to evaluate the role of protein hnRNPK in acute promyelocytic leukemia and the induction of cell differentiation granulocytic using cells NB4 and NB4-R2 human treated or not with ATRA in the presence or absence of the protein hnRNPK. The increase of this protein has been described in several tumors, but the possible participation of hnRNPK in the mechanism of leukemogenesis of APL and cell differentiation remains to be defined. Preliminary results show change in cellular distribution of hnRNPK NB4 cells subjected to treatment with ATRA, which indicates involvement of this protein in the process. It will be held hnRNPK silencing using RNA interference (shRNA) cells NB4 and NB4-R2 and they will be subjected to tests: cell proliferation, cell viability, sensitivity to ATRA / differentiation. (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)
GOTO, RENATA NISHIDA; SOBRAL, LAYS MARTIN; STRINGHETTA-PADOVANI, KARINA; GARCIA, CRISTIANA B.; DA SILVA, GABRIEL; VITEK, MICHAEL P.; LEOPOLDINO, ANDREIA MACHADO. Synergic effect of OP449 and FTY720 on oral squamous cell carcinoma. European Journal of Pharmacology, v. 882, SEP 5 2020. Web of Science Citations: 0.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
PADOVANI, Karina Stringhetta. Analysis of hnRNPK protein in cell lines NB4 and NB4-R2 of acute promyelocytic leukemia with emphasis in pathogenesis and cell differentiation by all-trans retinoic acid. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto Ribeirão Preto.

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