Myeloid cell leukemia 1 mRNA (MCL-1 mRNA) (MCL1 mRNA)

Myeloid cell leukemia 1 (MCL-1) mRNA is the transcript responsible for the synthesis of the MCL-1 protein, a critical anti-apoptotic member of the BCL-2 family (Source: UniProt P92431). The MCL-1 protein plays a pivotal role in promoting cell survival by inhibiting pro-apoptotic proteins such as BAX and BAK, thereby preventing mitochondrial outer membrane permeabilization (Source: PubMed 23863738). In many malignancies, including acute myeloid leukemia and multiple myeloma, MCL-1 mRNA is frequently overexpressed, contributing to tumor cell evasion of apoptosis and resistance to conventional chemotherapies (Source: PubMed 30135600). Targeting the mRNA directly using antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) offers a strategy to downregulate protein expression at the source, potentially overcoming resistance mechanisms associated with protein-level regulation. However, therapeutic development faces significant hurdles due to the essential role of MCL-1 in maintaining normal tissues; for instance, its deletion in mice leads to fatal heart failure, highlighting a major cardiotoxicity risk (Source: PubMed 23417613). Consequently, drugs like IONIS-MCL1Rx are designed to reduce MCL-1 levels in a controlled manner to achieve a therapeutic window in oncology (Source: Ionis Pharmaceuticals).

Other names

MCL1 transcriptMyeloid cell leukemia sequence 1 mRNAMCL-1 messenger RNABcl-2-related protein EAT/mcl1 mRNA

Antisense-mediated degradation of mRNA via RNase H recruitment or RNA interference (RNAi) leading to reduced translation of the MCL-1 anti-apoptotic protein (Source: PubMed 30135600).