{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMYBL1 is a potent transcriptional activator whose oncogenic potential has been elucidated in several central nervous system tumors. In pediatric low‐grade gliomas and isomorphic diffuse astrocytomas, recurrent genomic alterations in MYBL1—including partial duplications, truncations that disrupt its C‐terminal negative regulatory domain, and fusion events—result in constitutive activation of the protein. These alterations promote anchorage‐independent growth and help define molecular subgroups with distinct clinical outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn adenoid cystic carcinomas (ACCs) arising at diverse anatomical sites—including salivary gland, breast, tracheobronchial, skin, and the Bartholin’s gland—MYBL1 gene rearrangements serve as alternative oncogenic drivers. In several MYB‐fusion negative ACCs, MYBL1 is found either fused to NFIB or rearranged with other partners, leading to its overexpression. These findings indicate that MYBL1 alterations converge with MYB alterations in driving tumorigenesis in ACCs that otherwise share a similar histopathological phenotype."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMYBL1’s contribution to oncogenesis extends beyond gliomas and ACCs. In diffuse large B‐cell lymphoma, a two‐gene expression index incorporating MYBL1 has been shown to robustly classify cell‐of‐origin subtypes and predict patient outcomes. In hepatocellular carcinoma, MYBL1 overexpression drives angiogenesis by binding to and transcriptionally upregulating ANGPT2, thereby promoting neovascularization, metastasis, and reduced sensitivity to sorafenib. Furthermore, in triple‐negative breast cancer, MYBL1—located at the frequently altered 8q locus—appears to act in concert with other genes to facilitate tumor progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in malignant transformation, MYBL1 is also implicated in non‐tumorigenic processes. In colorectal adenocarcinoma models, epigenetic regulation via O-GlcNAc modifications at the MYBL1 promoter has been linked to altered expression levels that modulate cancer stem cell populations and tumor progression. In parallel, studies in vascular endothelial cells have demonstrated that MYBL1 supports cell migration, proliferation, and autophagic flux—processes that are critical in maintaining endothelial function and that, when dysregulated, contribute to atherosclerotic plaque development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDespite mounting evidence for its cancer-promoting activities in multiple tissues, the role of MYBL1 in renal cancer remains unclear, representing an important area for future investigation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lori A Ramkissoon, Peleg M Horowitz, Justin M Craig, et al. 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