Runt-related transcription factor 1; RUNX1 partner transcriptional co-repressor 1 fusion mRNA (RUNX1-RUNX1T1) (RUNX1-RUNX1T1)

RUNX1-RUNX1T1 fusion mRNA is the chimeric transcript resulting from the t(8;21)(q22;q22) chromosomal translocation, a defining genetic event in approximately 10% of adult acute myeloid leukemia (AML) cases (Source: National Cancer Institute). This fusion joins the DNA-binding domain of the Runt-related transcription factor 1 (RUNX1) with the nearly complete RUNX1 partner transcriptional co-repressor 1 (RUNX1T1) (Source: UniProt). The resulting fusion protein acts as a dominant-negative regulator, recruiting corepressors like histone deacetylases (HDACs) to RUNX1 target genes, thereby blocking myeloid differentiation and promoting leukemic transformation (Source: PubMed ID 22510870). As a therapeutic target, the mRNA is susceptible to sequence-specific degradation via RNA interference (siRNA) or antisense oligonucleotides, which can restore normal hematopoietic signaling in preclinical models (Source: PubMed ID 15150103). Clinically, the quantification of RUNX1-RUNX1T1 mRNA levels via RT-qPCR is the gold standard for monitoring minimal residual disease (MRD) and predicting clinical relapse (Source: PubMed ID 30617275). While direct mRNA-targeting drugs are largely in the experimental phase, the fusion's downstream epigenetic effects are targeted by HDAC inhibitors like vorinostat in clinical trials (Source: ClinicalTrials.gov). Challenges in targeting this molecule include the risk of affecting wild-type RUNX1, which is essential for normal blood cell development (Source: PubMed ID 12612653).

Other names

AML1-ETORUNX1-MTG8t(8;21) fusion transcriptCBFA2-ETORUNX1-RUNX1T1 fusion transcript

RNA interference (siRNA), antisense oligonucleotide-mediated degradation, or inhibition of the encoded fusion protein's recruitment of histone deacetylases (HDACs).