Internal deletion of BCOR reveals a tumor suppressor function for BCOR in T lymphocyte malignancies.

ABSTRACT: Recurrent inactivating mutations have been identified in various hematological malignancies in the X-linked BCOR gene encoding BCL6 corepressor (BCOR); however, its tumor suppressor function remains largely uncharacterized. We generated mice missing Bcor exon 4, expressing a variant BCOR lacking the BCL6-binding domain. Although the deletion of exon 4 in male mice (Bcor^ΔE4/y ) compromised the repopulating capacity of hematopoietic stem cells, Bcor^ΔE4/y thymocytes had augmented proliferative capacity in culture and showed a strong propensity to induce acute T-cell lymphoblastic leukemia (T-ALL), mostly in a Notch-dependent manner. Myc, one of the critical NOTCH1 targets in T-ALL, was highly up-regulated in Bcor^ΔE4/y

SUBMITTER: Tanaka T 

PROVIDER: S-EPMC5626398 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature