MLLT3 super elongation complex subunit (AF9)

MLLT3 super elongation complex subunit (AF9) is a protein encoded by the MLLT3 gene and acts as a critical component of the super elongation complex (SEC), which regulates the transition of paused to actively elongating RNA polymerase II and thereby controls rapid gene transcription[10][3]. MLLT3 is a highly conserved chromatin reader with a YEATS domain that acts as an epigenetic “reader” of acetylated and crotonylated histones, linking chromatin state to transcriptional activation[5][10]. It’s particularly important for the self-renewal and differentiation of hematopoietic stem and progenitor cells, maintaining their transcriptional program and appropriate histone methylation, such as H3K79me2[5][2][8]. MLLT3/AF9 also plays a role in cancers—including acute myeloid and lymphoid leukemias—where gene fusions involving MLLT3 drive oncogenic misregulation of transcriptional elongation[3][5][8]. The protein interacts with multiple regulators and co-factors, including DOT1L, BCOR, CBX8, BRD4, and AF4, and contributes to controlling developmental and stress-responsive gene expression[2][5][10][6]. - No approved drugs are currently known to target MLLT3 directly. - No validated patient selection or efficacy biomarkers or safety biomarker data are available, but caution is warranted because of its pivotal role in hematopoietic stem cell biology and oncogenic potential if disrupted.

Other names

AF9myeloid/lymphoid or mixed-lineage leukemia translocated to 3ALL1-fused gene from chromosome 9MLLT3