Analysis of Levamisole and Corticosteroids effect on the development of B-ALL in mice with the IL7R oncogenic mutation

• Grant number: 24/03902-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2024
• End date: August 31, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: José Andrés Yunes
• Grantee: Lucas André Giorgiani de Almeida
• Host Institution: Centro Infantil de Investigações Hematológicas Dr Domingos A Boldrini (CIB). Campinas , SP, Brazil

Abstract

Acute lymphoid leukemia (ALL) is a pathology that affects cells of the lymphoid lineage, and its cases can be classified as T-cell or B-cell ALL. Different factors are related to the leukemogenesis process of ALL, which can be induced by an abnormal immune response to common infections, lack of cell competition, fusions resulting from chromosomal rearrangements and lesions in transcription factors. Recently, it was reported that the gain-of-function mutation in the ± subunit of the interleukin 7 receptor (IL7R) also plays a role in the induction of leukemogenesis. This mutation increases cell viability by promoting up-regulation of the anti-apoptotic Bcl-2, resulting in a pre-leukemic stage that eventually develops into high-penetrance B-ALL. Due to Levamisole's ability to prevent the differentiation of new lymphoid lineage precursors and to induce the continuous division of neoplastic cells, and the ability of glucocorticoids to reduce cell competition by eliminating healthy pro- and pre-B cells, their administration may result in increased penetrance of ALL-B in IL7R mutants. Therefore, this project aims to analyze how the action of Levamisole and Corticosteroids interferes on the development and evolution of ALL-B.