Findings demonstrate that PTBP1 supports AML proliferation by fine-tuning the expression and splicing of AML-essential genes, providing a workflow for systematically annotating RNA-associated protein dependencies in cancer.
PTBP1 is established as a critical regulator of AML cell fitness and a clinically actionable therapeutic combination that exploits AML dependency on PTBP1-CDC42 signaling to enhance the efficacy of venetoclax-based regimens is identified.
SUMMARY Tumor suppressor p53 is a transcription factor mutated in ~50% of cancers. Somatic mutations in the DNA-binding domain abolish tumor suppression and thus lead to a loss-of-function activity, while a small subset of recurrent “hotspot” mutants have been shown to confer gain-of-function activities. Using an intei...
Wuyue Zhou, Alice Long, Cameron J. Douglas et al.· Cell Reports· 0 citations
This review integrates the molecular logic of splice-site selection with the cancer-specific mechanisms that perturb it, summarizes representative isoform switches across the hallmarks of cancer, evaluates emerging technologies and clinical biomarkers, and discusses the opportunities and constraints of translating spli...
Background Most transcriptomic studies in acute myeloid leukemia (AML) have focused on transcriptional regulation, whereas the clinical and biological relevance of translation initiation factors remains insufficiently defined. Eukaryotic translation initiation factor 2 subunit alpha (EIF2S1) is a key regulator of trans...
Xiaoying Hong, Yingying Huang, Wei Wu et al.· Frontiers in Oncology· 0 citations
This study uncovers a therapeutic vulnerable lncRNA-centric circuitry and provides compelling preclinical evidence for the development and application of a novel RNA targeting-LNP based therapy for treatment of myeloid leukemia.
Zhenggen Jin, Brendan D. Ma, Karen Y. T. Chan et al.· bioRxiv· 0 citations