GLYCOCORTICOID SENSITIVITY AND ITS RELATIONSHIP WITH THE COMPONENTS OF THE METABOLIC SYNDROME IN PATIENTS TREATED FOR CHILDHOOD ACUTE LYMPHOCYTIC LEUKEMIA

• Grant number: 18/21342-0
• Support Opportunities: Regular Research Grants
• Duration: March 01, 2019 - April 30, 2022
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Adriana Aparecida Siviero Miachon
• Grantee: Adriana Aparecida Siviero Miachon
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: ANA VIRGINIA LOPES DE SOUSA ; Angela Maria Spinola Castro ; Antonio de Miranda ; Carlos Alberto Longui ; Eunice Mayumi Suenaga

Abstract

In patients treated for childhood acute lymphocytic leukemia (ALL), the aim is to determine the components of the metabolic syndrome, including central obesity, lipids, blood pressure and glucose/insulin, to assess glucocorticoid (GC) sensitivity through sensitivity tests and in vitro measurements to evaluate polymorphic variants/isoforms of the GC receptor (GR) and and to correlate clinical and metabolic profiles with GC sensitivity. The proposal is to evaluate 40 patients treated for childhood ALL, both post-pubertal and at least two years out of therapy, according to clinical, disease-related and treatment characteristics, anthropometric variables (weight, height and body mass index), adiposity indexes (circumferences and their relationships, fat mass by dual energy X-ray absorptiometry and abdominal fat by abdominal tomography), endocrine-metabolic profile (lipids and insulin resistance), tests (0.25 mg overnight oral dexamethasone suppression test and very low dose intravenous dexamethasone suppression test), determination of polymorphic variants of GR and mRNA quantification of its GR-alpha processing variant by quantitative real-time polymerase chain reaction (qrt-PCR). It is known that GC sensitivity determined by mRNA expression of different isoforms and/or the presence of specific GR polymorphisms is one of the factors involved in the response to treatment and an important prognostic factor in ALL. It is speculated if it also represents a mechanism of increased risk for cardiovascular disease in this subgroup of patients. (AU)