A noncoding mutation in the NOTCH1 gene initiates oncogenic NOTCH signaling via wild-type NICD stabilization in CLL.

ABSTRACT:

Abstract

Chronic lymphocytic leukemia (CLL) is the most common chronic blood cancer in adults. Active NOTCH signaling in CLL is associated with poorer prognosis. Importantly, patients with CLL with NOTCH1 noncoding mutations in the 3' untranslated region (3'UTR) manifested with a more aggressive disease course even compared with those with mutations in the NOTCH1 coding region. Here, we comprehensively characterize a cryptic splice acceptor site in the 3'UTR of the NOTCH1 gene being converted into a stronger site. The functional consequences of the resulting NOTCH1 protein variants depend on the exact localization of the splice site, the used open reading frame, and the appearance of the next stop codon. The most frequent 3'UTR mutation (g.139390152, A>G) generates a novel NOTCH1 p

SUBMITTER: Guo M 

PROVIDER: S-EPMC12883854 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature