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PML-RARA mutations and ATRA resistence in pediatric Acute Promielocytic Leukemia

Grant number: 20/09528-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2020
Effective date (End): October 31, 2021
Field of knowledge:Health Sciences - Medicine
Principal researcher:José Andrés Yunes
Grantee:Beatriz Mendes Galvão
Home Institution: Centro Infantil de Investigações Hematológicas Dr Domingos A Boldrini (CIB). Campinas , SP, Brazil

Abstract

Leukemias are hematological neoplastic diseases, that are characterized by uncontrolledproliferation of hematopoietic cells and are classified according to the phenotype of theaffected cell. In this study we will emphasize acute promyelocytic leukemia (APL),belonging to the group of acute myeloid leukemias (AML), subgroup M3 or M3 variant. APLis characterized by chromosomal translocation t(15;17) that involves PML (15q24.1) andRARA (17q21.2) genes and results in the formation of chimeric transcript and PML-RARAfusion protein. t(15;17) is found in 95% of patients with APL and the treatment of thisleukemia is based on the use of all-trans retinoic acid combined with anthracyclinechemotherapy. More recently arsenic trioxide has been incorporated into the treatment withconsiderable improvement in therapeutic success. Some patients have poor response orresistance to treatment with ATRA and studies suggest that mutations in PML-RARA fusiontranscrips may be responsible for this behavior. Thus the present study aims to analyze andidentify possible mutations in PML-RARA APL t(15;17) positive cases admitted for treatmentat Boldrini children's center between 2000 and 2020. The analyzes will be performed throughqualitativr PCR and sanger genetic sequencing. Results will be correlated patients' responsesto treatment.

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