MLLT (Mixed Lineage Leukemia Translocated)阻害剤

The MLLT (Mixed Lineage Leukemia Translocated) family, part of the broader MLL (Mixed Lineage Leukemia) network, plays a crucial role in hematopoiesis and leukemogenesis. Members of the MLLT family, such as MLLT1, MLLT3, and MLLT10, are frequently involved in chromosomal translocations associated with various forms of leukemia, particularly acute lymphoblastic and myeloid leukemias. These translocations often result in the formation of fusion proteins combining MLL with MLLT family proteins, leading to altered gene expression. The MLLT proteins, through these fusions, contribute to the dysregulation of gene transcription, particularly affecting genes involved in cell growth and differentiation. Such dysregulation is primarily mediated by altered histone methylation patterns, as MLLT proteins interact with chromatin-modifying complexes, influencing epigenetic regulation. The critical role of MLLT family signaling in the pathogenesis of leukemia makes it a significant target for developing targeted therapies and understanding cancer biology.

MLLT (Mixed Lineage Leukemia Translocated) family inhibitors are designed to interfere with the aberrant protein-protein interactions and epigenetic modifications induced by MLLT fusion proteins. For example, inhibitors that disrupt the interaction between MLLT fusion proteins and key cofactors like DOT1L or menin can hinder the leukemogenic process by normalizing gene expression patterns. Additionally, targeting the downstream effects of MLLT translocations, such as through histone modification enzymes like HDACs or bromodomain-containing proteins, can also be effective.