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Study of the epidermal growth factor receptor inhibitor gefitinib in acute myeloid leukemia cell line

Grant number: 17/00775-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2017
Effective date (End): June 30, 2018
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Luciana Yamamoto de Almeida
Grantee:Nayara Ferreira de Abreu
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Gefitinib is an epidermal growth factor receptor (EGFR) inhibitor that was originally approved by the Food and Drug Administration (FDA) for the treatment of non-small cell lung cancer (NSCLC). Studies evaluating the expression of EGFR in hematopoietic precursors do not present unanimous results. Patients with synchronous NSCLC and acute myeloid leukemia (AML) treated with gefitinib had regression of both neoplasms, although the myeloblasts of these patients were EGFR negative. On the other hand, it has recently been shown that around 15% of AML patients express EGFR at the protein level and functionally active. Mutations in the NPM1 gene (Nucleophosmin) correspond to the most frequent type of genetic alteration in adult AML patients, occurring around 30%, and are responsible for the blockade in differentiation and for promoting cell proliferation. Recently, studies have demonstrated the therapeutic efficacy of the association of EGFR inhibitors with all-trans retinoic acid (ATRA) in reversing the undifferentiated phenotype of AML cell lines, as well as by inhibiting cell proliferation. In addition, a clinical study has shown that the combination of ATRA to chemotherapy has provided benefits in overall relapse-free survival of adult AML patients with NPM1 mutation. However, there are no reports on the possible effects of EGFR inhibitors combined with ATRA in the treatment of AML with mutation in NPM1. Therefore, in the present work, we intend to evaluate the effects of gefitinib treatment alone or associated with ATRA on the proliferation and differentiation rates of NPM1-mutated OCI-AML3 cell line. In the future, the results of this study may contribute to the improvement of NPM1-mutated AML patients' clinical outcomes. (AU)