Anlotinib suppresses MLL-rearranged acute myeloid leukemia cell growth by inhibiting SETD1A/AKT-mediated DNA damage response.

ABSTRACT: Leukemias driven by chromosomal translocation of the mixed-lineage leukemia (MLL) gene are highly prevalent in hematological malignancy. The poor survival rate and lack of effective targeted therapy for patients with MLL-rearranged (MLL-r) leukemias emphasize an urgent need for improved knowledge and novel therapeutic approaches for these malignancies. The present study aimed to investigate the potential effectiveness and mechanism of Anlotinib, a novel receptor tyrosine kinase inhibitor, in MLL-r acute myeloid leukemia (AML). The findings revealed that Anlotinib significantly inhibited the growth of MLL-r AML cells in both in vivo and a murine xenograft model. RNA sequencing identified that multiple genes involved in DNA damage response were responsible for Anlotinib activity. To f

SUBMITTER: Chen J 

PROVIDER: S-EPMC8014360 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature