Effect of vitamin C administration on the clonal architecture of myeloid neoplasms

• Grant number: 24/11135-9
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: February 01, 2025
• End date: January 31, 2028
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Sara Teresinha Olalla Saad
• Grantee: João Vitor Facco
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Somatic mutations in genes responsible for epigenetic modulation seem to occur years before the diagnosis of acute myeloid leukemia (AML). Recently, the role of ascorbic acid (vitamin C) in regulating the activity of TET2 (ten-eleven-translocation 2), an important enzyme that catalyzes the hydroxylation of 5-methylcytosine, whose gene is frequently mutated in aging and myeloid neoplasms, has been described. Given that individuals with idiopathic cytopenias, myelodysplastic syndrome, and chronic myelomonocytic leukemia can develop AML, this study aims to determine whether vitamin C modifies the mutation profile in these diseases and, ultimately, delays or prevents the onset of AML. For this study, patients with clonal cytopenia of undetermined significance, low-risk myelodysplastic syndrome, and chronic myelomonocytic leukemia will be randomized to receive vitamin C or placebo, with subsequent monitoring of hematological parameters, clonal architecture, and methylcytosine hydroxylation. The data from this study may provide a basis for prevention strategies in populations at high risk of developing AML