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Detection and functional analysis of Tumor-Associated Macrophages (TAM) in a transgenic model of acute promyelocytic leukemia (APL).

Grant number: 15/09228-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2015
Effective date (End): November 16, 2020
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Eduardo Magalhães Rego
Grantee:Isabel Weinhauser
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):17/25358-6 - Detection and functional analysis of Tumor Associated Macrophages in Acute Promyelocytic mouse model, BE.EP.DR

Abstract

Acute promyelocitic leukemia is a hematological cancer form driven by the emergence and proliferation of granulocyte precursor cells, which in 90 % of the cases is caused by the translocation, of the retinoic acid receptor ± (RAR±) gene on chromosome 17 and the promyelocitic leukemia protein (PML) on chromosome 15. Due to this translocation APL patients exhibit a chimeric PML-RAR±/RAR±-PML protein becoming unresponsive towards the RAR± ligand retinoic acid (RA), which results in transcriptional silencing and subsequently prevents granulocyte differentiation. However the induction of pharmacological doses of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are capable of reinitiating transcriptional activity and thus represent the major therapeutic approach for APL treatment. Yet the emergence of tumor bulk is not solely facilitated by mutations preventing regulation of cellular growth and accurate induction of apoptosis but also depend on a pro-tumorigenic environment. Such pro-tumorigenic environment is characterized by an anti-inflammatory immune response providing the oncogenic cells with ideal circumstances to expand. Macrophages are amongst other immune cells known to be capable of attenuating immune response via their ability to differentiate into M1 and M2 cells triggering pro and anti-inflammatory response respectively. Taking into regards that many cancer types display predominant presence of M2 macrophages, we intended to focus in this research proposal on the detection and impact of M2 macrophages in (APL) formation. For this purpose we are eager to procure a general outline on hematopoiesis, concentrate on the emergence of APL and proceed with an overview on the immune system with an increased alertness on the function of macrophages and their influence on cancer genesis.

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)
WEINHAUSER, ISABEL; PEREIRA-MARTINS, DIEGO A.; ORTIZ, CESAR; SILVEIRA, DOUGLAS R.; SIMOES, LUISE A. A.; BIANCO, THIAGO M.; ARAUJO, CLEIDE L.; KOURY, LUISA C.; MELO, RAUL A. M.; BITTENCOURT, ROSANE I.; PAGNANO, KATIA; PASQUINI, RICARDO; NUNES, ELENAIDE C.; FAGUNDES, EVANDRO M.; GLORIA, ANA B.; KERBAUY, FABIO; CHAUFFAILLE, MARIA DE LOURDES; KEATING, ARMAND; TALLMAN, MARTIN S.; RIBEIRO, RAUL C.; DILLON, RICHARD; GANSER, ARNOLD; LOWENBERG, BOB; VALK, PETER; LO-COCO, FRANCESCO; SANZ, MIGUEL A.; BERLINER, NANCY; AMMATUNA, EMANUELE; LUCENA-ARAUJO, ANTONIO R.; SCHURINGA, JAN JACOB; REGO, EDUARDO M. Reduced SLIT2 is Associated with Increased Cell Proliferation and Arsenic Trioxide Resistance in Acute Promyelocytic Leukemia. CANCERS, v. 12, n. 11 NOV 2020. Web of Science Citations: 1.

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