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

Bcl-2-like protein 11 (BCL2L11), commonly known as BIM, is a pro-apoptotic member of the Bcl-2 family that plays a critical role in the intrinsic pathway of programmed cell death (UniProt P55957). The BCL2L11 mRNA is a significant therapeutic target, particularly due to a common genomic deletion polymorphism in intron 2 found in approximately 12 percent of East Asian populations (PubMed: 22426308). This polymorphism results in the preferential splicing of mRNA isoforms, such as BIM-gamma, that lack the pro-apoptotic BH3 domain, leading to intrinsic resistance to tyrosine kinase inhibitors (TKIs) in cancers such as non-small cell lung cancer and chronic myeloid leukemia (PubMed: 25713334). Therapeutic strategies targeting BCL2L11 mRNA involve the use of antisense oligonucleotides (ASOs) or splicing-switching oligonucleotides to redirect splicing toward the functional, BH3-containing isoforms like BIM-EL (PubMed: 25713334). By restoring the production of functional BIM protein, these therapies aim to sensitize cancer cells to apoptosis and overcome drug resistance. Beyond oncology, BIM mRNA levels and its alternative splicing are also investigated in the context of autoimmune diseases and lymphocyte homeostasis (NCBI Gene: 10018).

Other names

BIM mRNABcl-2-related ovarian death gene mRNABOD mRNABcl2-L-11 mRNA

Modulation of alternative splicing to restore functional BH3-containing BIM isoforms or direct knockdown of specific mRNA variants to overcome apoptosis resistance.