Overexpression of Lmo2 initiates T-lymphoblastic leukemia via impaired thymocyte competition.

ABSTRACT: Cell competition has recently emerged as an important tumor suppressor mechanism in the thymus that inhibits autonomous thymic maintenance. Here, we show that the oncogenic transcription factor Lmo2 causes autonomous thymic maintenance in transgenic mice by inhibiting early T cell differentiation. This autonomous thymic maintenance results in the development of self-renewing preleukemic stem cells (pre-LSCs) and subsequent leukemogenesis, both of which are profoundly inhibited by restoration of thymic competition or expression of the antiapoptotic factor BCL2. Genomic analyses revealed the presence of Notch1 mutations in pre-LSCs before subsequent loss of tumor suppressors promotes the transition to overt leukemogenesis. These studies demonstrate a critical role for impaired cell competiti

SUBMITTER: Abdulla HD 

PROVIDER: S-EPMC10037042 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature