Bcl-2-like protein 11 mRNA (BCL2L11 mRNA) (BCL2L11 mRNA)

Bcl-2-like protein 11 (BIM) mRNA is the transcript of the BCL2L11 gene, which encodes a key pro-apoptotic protein within the BH3-only subfamily of the Bcl-2 family (UniProt P55957). BIM is essential for initiating the intrinsic apoptotic pathway in response to various stimuli, including growth factor withdrawal and treatment with tyrosine kinase inhibitors (TKIs). In clinical oncology, a specific germline deletion polymorphism in the BIM gene results in alternative splicing that favors the production of non-apoptotic isoforms, leading to intrinsic resistance to TKIs in patients with EGFR-mutant lung cancer or BCR-ABL-positive leukemia (PMID: 22426308). Targeting BIM mRNA involves strategies to restore the production of the functional, pro-apoptotic BIM-EL isoform. These strategies include using antisense oligonucleotides to correct splicing or HDAC inhibitors like Vorinostat to upregulate overall transcript levels (PMID: 25103565, PMID: 23612973). Consequently, BIM mRNA levels and its splicing patterns serve as critical biomarkers for predicting patient response to targeted therapies. BIM is also involved in the response to other stressors, such as endoplasmic reticulum stress and cytokine deprivation. Therapeutic modulation of BIM mRNA is an active area of drug development aimed at overcoming treatment resistance in various malignancies.

Other names

BIM mRNABcl-2-related ovarian death gene mRNABOD mRNABCL2L11 transcript

Induction of mRNA expression through histone deacetylase inhibition and modulation of pre-mRNA splicing to favor pro-apoptotic isoforms.