Loss of thymocyte competition underlies the tumor suppressive functions of the E2a transcription factor in T-ALL.

ABSTRACT: T lymphocyte acute lymphoblastic leukemia (T-ALL) is frequently associated with increased expression of the E protein transcription factor inhibitors TAL1 and LYL1. In mouse models, ectopic expression of TAL1 or LYL1 in T cell progenitors, or inactivation of E2A, is sufficient to predispose mice to develop T-ALL. How E2A suppresses thymocyte transformation is currently unknown. Here, we show that early deletion of E2a, prior to the DN3 stage, was required for robust leukemogenesis and was associated with alterations in thymus cellularity, T cell differentiation, and gene expression in immature CD4⁺CD8⁺ thymocytes. Introduction of wild-type thymocytes into mice with early deletion of E2a prevented leukemogenesis, or delayed disease onset, and impacted the expression of

SUBMITTER: Parriott G 

PROVIDER: S-EPMC12523820 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature