{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAF1q, also known as MLLT11, is a multifaceted gene originally identified as an MLL fusion partner that plays diverse roles in both cancer and normal development. Elevated expression of AF1q/MLLT11 has been implicated in driving malignancy through activation of several signaling cascades. For example, aberrant AF1q expression promotes breast cancer metastasis by modulating integrin‐mediated invasion and by engaging Wnt/TCF7 pathways, while its up‐regulation in acute myeloid leukemia has been associated with poor clinical outcomes. Moreover, AF1q/MLLT11 can activate PDGF/PDGFR‐mediated Src and STAT3 signaling, further contributing to oncogenic progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn various solid tumors and hematologic malignancies, high AF1q/MLLT11 expression correlates with aggressive features such as enhanced proliferation, increased epithelial–mesenchymal transition, invasion, and metastasis. In colorectal, esophageal, adenoid cystic, and breast cancers, AF1q/MLLT11 modulates key oncogenic pathways—including AKT, STAT3, and Wnt—as well as downstream effectors like CD44 and matrix metalloproteinases. Such activities not only support tumor growth and metastatic colonization but can also contribute to the enrichment of a stem‐like cell population in the primary tumor."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAF1q/MLLT11 also plays an important role in regulating apoptosis and modulating therapeutic responses. In several cancer cell models—including squamous carcinoma lines—AF1q/MLLT11 has been shown to enhance drug- and radiation-induced apoptosis by upregulating proapoptotic factors such as BAD, an effect that is mediated at least in part by NF-κB. These proapoptotic influences underscore the dualistic nature of AF1q/MLLT11, which in some contexts can promote cell death in response to treatment while in others it supports oncogenic survival signals."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its oncogenic activities, AF1q/MLLT11 is involved in normal cellular differentiation and homeostasis. In hematopoietic progenitors, enforced AF1q expression favors T-cell rather than B-cell differentiation by enhancing Notch signaling, while studies in neural precursor cells have documented marked upregulation during neuronal lineage commitment. In addition, AF1q/MLLT11 protein levels are tightly regulated through chaperone-mediated autophagy via interactions with HSPA8 and LAMP-2A, ensuring appropriate protein turnover during differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, emerging evidence links AF1q/MLLT11 to nonmalignant conditions as well. Genetic interaction studies have suggested that polymorphisms in AF1q may contribute to susceptibility to disorders such as schizophrenia, while loss of proper AF1q regulation has been associated with hearing impairment through disrupted REST-mediated repression and with altered cell cycle control and adhesion in endometriosis. These findings highlight the dual roles of AF1q/MLLT11 in both pathological and physiological processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hsingchi J Lin, Kara M Shaffer, Zairen Sun, et al. 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