Eleven-nineteen-leukemia protein (ENL) (ENL)

The Eleven-nineteen-leukemia protein (ENL), also known as MLLT1, is a critical chromatin reader and a key component of the Super Elongation Complex (SEC) (UniProt Q03111; thesgc.org). It contains a conserved YEATS domain that specifically recognizes acetylated lysine residues on histone H3, such as H3K9ac, H3K18ac, and H3K27ac, thereby recruiting the transcriptional machinery to active gene promoters (nih.gov; mdpi.com). ENL plays a pivotal role in regulating RNA polymerase II elongation and is essential for the maintenance of oncogenic gene expression programs (patsnap.com; biorxiv.org). In clinical contexts, ENL is frequently involved in chromosomal translocations, most notably the t(11;19) translocation that creates the MLL-ENL fusion protein, a driver of aggressive acute myeloid and lymphoid leukemias (nih.gov; news-medical.net). Additionally, mutations in the ENL YEATS domain are associated with the development of Wilms tumor, the most common pediatric kidney cancer (nih.gov; researchgate.net). Therapeutic targeting of ENL focuses on small-molecule inhibitors and proteolysis-targeting chimeras (PROTACs) that disrupt the YEATS domain's interaction with chromatin (acs.org; medchemexpress.com). These agents lead to the selective downregulation of leukemia-promoting genes like MYC and HOXA9 while showing limited toxicity to normal hematopoietic cells (biorxiv.org; nih.gov). Current research is focused on improving the potency and pharmacokinetic properties of these inhibitors for clinical application (acs.org).

Other names

MLLT1LTG19YEATS1Myeloid/lymphoid or mixed-lineage leukemia; translocated to, 1

Inhibition of the YEATS domain to prevent recruitment to acetylated histones; Targeted protein degradation of ENL via PROTACs (nih.gov; acs.org).