{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRUNX1T1 (also known as ETO, MTG8, or CBFA2T1) normally functions as a transcriptional corepressor in hematopoietic cells. In the context of the t(8;21) chromosomal translocation, its fusion with the RUNX1 gene produces the AML1‐ETO oncoprotein that interferes with normal RUNX1‐mediated transcription. This chimeric protein retains most of the RUNX1T1 moiety, which provides key protein–protein interaction domains that recruit histone deacetylases and other chromatin remodeling complexes. Such interactions repress the transcription of critical target genes involved in differentiation, cell‐cycle control, microRNA expression, and stem cell regulation. In addition, alternative splicing events (e.g. AML1‐ETO9a formation) and oligomerization mediated by conserved domains of RUNX1T1 influence the potency of the oncogenic fusion protein, altering its capacity to block myeloid differentiation and promote self‐renewal."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role as a static scaffold for corepressor recruitment, RUNX1T1‐derived sequences contribute to complex epigenetic regulation. In AML1‐ETO, the RUNX1T1 portion facilitates the binding of chromatin modifiers such as p300, HDACs, and DNA methyltransferases—which results in posttranslational modifications including acetylation and heterochromatic silencing of target loci, such as regulatory microRNA genes. These epigenetic events modify the chromatin landscape at critical promoters and enhancers, leading to repression of differentiation–promoting genes and establishment of a self–renewing, leukemogenic state."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "37"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRUNX1T1’s role is further elaborated by its interactions with additional transcription factors and signaling pathways that determine leukemic cell fate. Its incorporation in the fusion protein is linked to altered cellular responses that involve deregulated cell proliferation, survival, and self–renewal capacity—and these effects are often augmented by cooperating oncogenic mutations and aberrant signaling (for example, via c–KIT or other pathways). Moreover, the fusion protein’s capacity to interact with factors such as E proteins, AP–1, and core components of the Notch pathway underscores its versatility in reprogramming gene networks. These multifaceted functions collectively underpin the pathogenic contribution of RUNX1T1 in acute myeloid leukemia and highlight its potential as a therapeutic target in hematologic malignancies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "38", "end_ref": "43"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Felicetto Ferrara, Luigi Del Vecchio "}, {"type": "b", "children": [{"type": "t", "text": "Acute myeloid leukemia with t(8;21)/AML1/ETO: a distinct biological and clinical entity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Haematologica (2002)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11869944"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11869944"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Alex Tonks, Lorna Pearn, Amanda J Tonks, et al. 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