{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nVENTX is a human homeobox transcription factor that plays a multifaceted role in hematopoietic cell fate determination. In normal hematopoiesis, VentX acts as a modulator of the Wnt/β-catenin signaling pathway, functioning as a negative regulator of cell proliferation and influencing the balance between myeloid and lymphoid lineage commitment. Aberrant expression of VentX has been observed in hematologic malignancies, whereby its overexpression in progenitor cells promotes myeloid differentiation at the expense of lymphoid development, and its suppression leads to the expansion of primitive hematopoietic stem/multipotent progenitor pools. Such findings underscore the importance of VentX in maintaining proper cell cycle regulation and lineage specification in the hematopoietic system."}, {"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 the realm of immune regulation, VentX is critical for the differentiation and functional activation of several immune cell types. It is indispensable for the terminal differentiation and proinflammatory activation of macrophages, where it governs the expression of key molecules such as the M-CSF receptor. Moreover, VentX promotes dendritic cell differentiation and maturation—partially through modulation of IL-6 expression—and its downregulation in tumor-associated macrophages (TAMs) is linked to an immunosuppressive tumor microenvironment. Restoration of VentX expression in TAMs has been shown to enhance phagocytosis, steer macrophage polarization toward an M1 phenotype, and thereby reprogram the tumor microenvironment toward anti-tumor immunity, as evidenced in models of colon cancer and pancreatic ductal adenocarcinoma."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nVentX also appears to function as a tumor suppressor. It directly activates key checkpoints in the p53-p21 and p16^INK4a^-Rb pathways, thereby triggering irreversible cell cycle arrest and cellular senescence in certain cancer contexts, including lymphocytic leukemia. Ectopic expression of VentX in cancer cells not only diminishes their proliferative and survival capabilities via p53-independent mechanisms but also sensitizes them to chemotherapeutic agents. Conversely, in the context of erythroid differentiation, constitutive VentX expression can perturb normal differentiation processes and contribute to leukemogenesis, particularly when coexpressed with other oncogenes. These observations highlight VentX as a promising target for cancer prevention and therapeutic intervention."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hong Gao, Yi Le, Xiaoming Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "VentX, a novel lymphoid-enhancing factor/T-cell factor-associated transcription repressor, is a putative tumor suppressor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-09-2668"}], "href": "https://doi.org/10.1158/0008-5472.CAN-09-2668"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20028861"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20028861"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Vijay P S Rawat, Natalia Arseni, Farid Ahmed, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The vent-like homeobox gene VENTX promotes human myeloid differentiation and is highly expressed in acute myeloid leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1001878107"}], "href": "https://doi.org/10.1073/pnas.1001878107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20833819"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20833819"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hong Gao, Xiaoming Wu, Yan Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Suppression of homeobox transcription factor VentX promotes expansion of human hematopoietic stem/multipotent progenitor cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.383018"}], "href": "https://doi.org/10.1074/jbc.M112.383018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22791709"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22791709"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xiaoming Wu, Hong Gao, Weixiong Ke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The homeobox transcription factor VentX controls human macrophage terminal differentiation and proinflammatory activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI45556"}], "href": "https://doi.org/10.1172/JCI45556"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21670496"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21670496"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xiaoming Wu, Hong Gao, Ronald Bleday, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Homeobox transcription factor VentX regulates differentiation and maturation of human dendritic cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.509158"}], "href": "https://doi.org/10.1074/jbc.M113.509158"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24706756"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24706756"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yi Le, Hong Gao, Ronald Bleday, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The homeobox protein VentX reverts immune suppression in the tumor microenvironment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-04567-0"}], "href": "https://doi.org/10.1038/s41467-018-04567-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29872044"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29872044"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yi Le, Hong Gao, William Richards, et al. "}, {"type": "b", "children": [{"type": "t", "text": "VentX expression in tumor-associated macrophages promotes phagocytosis and immunity against pancreatic cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JCI Insight (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/jci.insight.137088"}], "href": "https://doi.org/10.1172/jci.insight.137088"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32573491"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32573491"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Xiaoming Wu, Hong Gao, Weixiong Ke, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "VENTX induces expansion of primitive erythroid cells and contributes to the development of acute myeloid leukemia in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.13563"}], "href": "https://doi.org/10.18632/oncotarget.13563"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27888632"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27888632"}]}]}]}