A cell competition-based small molecule screen identifies a novel compound that induces dual c-Myc depletion and p53 activation.

ABSTRACT: Breakpoint Cluster Region-Abelson kinase (BCR-Abl) is a driver oncogene that causes chronic myeloid leukemia and a subset of acute lymphoid leukemias. Although tyrosine kinase inhibitors provide an effective treatment for these diseases, they generally do not kill leukemic stem cells (LSCs), the cancer-initiating cells that compete with normal hematopoietic stem cells for the bone marrow niche. New strategies to target cancers driven by BCR-Abl are therefore urgently needed. We performed a small molecule screen based on competition between isogenic untransformed cells and BCR-Abl-transformed cells and identified several compounds that selectively impair the fitness of BCR-Abl-transformed cells. Interestingly, systems-level analysis of one of these novel compounds, DJ34, revealed that it in

SUBMITTER: Tadele DS 

PROVIDER: S-EPMC7948465 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature