Inhibition of the m⁶A reader IGF2BP2 as a strategy against T-cell acute lymphoblastic leukemia.

ABSTRACT: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignant leukemia with extremely limited treatment for relapsed patients. N6-methyladenosine (m⁶A) reader insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) participates in the initiation and growth of cancers by communicating with various targets. Here, we found IGF2BP2 was highly expressed in T-ALL. Gain and loss of IGF2BP2 demonstrated IGF2BP2 was essential for T-ALL cell proliferation in vitro and loss of IGF2BP2 prolonged animal survival in a human T-ALL xenograft model. Mechanistically, IGF2BP2 directly bound to T-ALL oncogene NOTCH1 via an m⁶A dependent manner. Furthermore, we identified a small-molecule IGF2BP2 inhibitor JX5 and treatment of T-ALL with JX5 showed similar functions as knoc

SUBMITTER: Feng P 

PROVIDER: S-EPMC9417996 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature