| Grant number: | 17/02400-7 |
| Support type: | Scholarships in Brazil - Doctorate |
| Effective date (Start): | June 01, 2017 |
| Effective date (End): | February 28, 2021 |
| Field of knowledge: | Health Sciences - Medicine |
| Cooperation agreement: | Coordination of Improvement of Higher Education Personnel (CAPES) |
| Principal Investigator: | José Andrés Yunes |
| Grantee: | Juliana Ronchi Corrêa |
| Home Institution: | Centro Infantil de Investigações Hematológicas Dr Domingos A Boldrini (CIB). Campinas , SP, Brazil |
| Associated scholarship(s): | 20/11380-2 - Dissecting the RAS/MEK/ERK pathway downstream the oncogenic IL7R in acute lymphoblastic leukemia, BE.EP.DR |
Abstract Acute lymphocytic leukemia (ALL) is the most common type of cancer in childhood. Eighty five percent of ALL originate from B-cell precursors (B-ALL) and 15% from thymocytes (T-ALL). Different chromosomal alterations and oncogenic mutations are known to interrupt the normal process of cell differentiation and/or induce proliferation. We have recently described oncogenic mutations in the IL7R gene in T-ALL. Mutations of IL7R were also found, but less frequently, in 6.5% of B-ALL belonging to the BCR/ABL1-like subtype. This subtype of ALL has a dismal prognosis. Interestingly, about 70% of the BCR/ABL1-like ALLs carry mutations that, like the IL7R ones, activate the JAK-STAT pathway. Studies have shown that IL7R is required for efficient differentiation of B220 + CD43 + (pro-B) and B220 + CD43- (pre-B) cells. Our preliminary results with a knockin mouse model of the IL7R mutation revealed the occurrence of B-ALL in the animals. In this project we propose to study the IL7R-dependent leukemogenesis process in B lymphocyte precursors. Obtained ALLs will be characterized in terms immunophenoptype, immunoglobulin rearrangement and clonality, engraftment and progression in second recipients. The presence of concurring genetic alterations, gene expression profile and the activation of the different IL7R signal transduction pathways will be evaluated aiming to verify the similarities with a BCR/ABL1-like ALL in humans. (AU) | |