Abstract 2035 Mechanistic determination of the role of a mixed lineage leukemia protein containing a partial tandem duplication (MLLPTD) in MDS and AML

The mixed lineage leukemia (MLL) methyltransferase gene is a member of the trithorax group family of factors and plays a significant role in development and hematopoiesis. In a healthy context, MLL is a lysine methyltransferase that catalyzes trimethylation of histone H3 at lysine 4 (K3K4me3), facilitating a transcriptionally permissive environment at promoters. However, defects in MLL are associated with hematopoietic malignancies. One class of MLL-related cancers involves rearrangements of the MLL N-terminal region that manifest as in-frame partial tandem duplications (PTD) of MLL's N-term domains, resulting in an elongated protein with aberrant function, with the most common form of MLLPTD containing duplications of exons 2-6.