{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:45:00Z","timestamp":1791096300191,"version":"4.1.0"},"reference-count":64,"publisher":"National Academy of Sciences","issue":"5","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,2,29]]},"abstract":"<jats:p>\n                    We have identified a gene at 11q23, telomeric to\n                    <jats:italic>MLL<\/jats:italic>\n                    , that encodes a guanine nucleotide exchange factor (GEF). This gene is transcribed into a 9.5-kb mRNA containing a 4.6-kb ORF. By Northern analysis, it was found to be expressed in all human tissues examined including peripheral blood leukocytes, spleen, prostate, testis, ovary, small intestine, colon, and minimally in thymus. Analysis of the predicted protein sequence indicates that it has strong homology to several members of the family of Rho GEFs that includes such oncogenes as\n                    <jats:italic>Dbl<\/jats:italic>\n                    ,\n                    <jats:italic>Vav<\/jats:italic>\n                    ,\n                    <jats:italic>Tiam<\/jats:italic>\n                    , and\n                    <jats:italic>Bcr<\/jats:italic>\n                    . A patient with primary acute myeloid leukemia (AML) and a karyotype of 51,XY,+8,+19,+3mar was found to have the 5\u2032 end of\n                    <jats:italic>MLL<\/jats:italic>\n                    at exon 6 fused in-frame with the 3\u2032 end of almost the entire ORF of this gene, which we named\n                    <jats:italic>LARG<\/jats:italic>\n                    for leukemia-associated Rho GEF. Transcriptional orientation of both genes at 11q23 is from centromere to telomere, consistent with other data that suggest the\n                    <jats:italic>MLL-LARG<\/jats:italic>\n                    fusion resulted from an interstitial deletion rather than a balanced translocation.\n                    <jats:italic>LARG<\/jats:italic>\n                    does not appear to have any homology with other\n                    <jats:italic>MLL<\/jats:italic>\n                    partner genes reported thus far. Thus,\n                    <jats:italic>LARG<\/jats:italic>\n                    represents an additional member of the GEF family and a novel\n                    <jats:italic>MLL<\/jats:italic>\n                    fusion partner in acute myeloid leukemia.\n                  <\/jats:p>","DOI":"10.1073\/pnas.040569197","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:41:48Z","timestamp":1027680108000},"page":"2145-2150","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":195,"title":["Identification of a gene at 11q23 encoding a guanine nucleotide exchange factor: Evidence for its fusion with\n                    <i>MLL<\/i>\n                    in acute myeloid leukemia"],"prefix":"10.1073","volume":"97","author":[{"given":"Peter J.","family":"Kourlas","sequence":"first","affiliation":[{"name":"The Division of Hematology and Oncology, Department of Internal Medicine, The Comprehensive Cancer Center, and The Division of Human Cancer Genetics, Department of Molecular Virology, Immunology, and Medical Genetics, and Department of Pathology, The Ohio State University College of Medicine and Public Health, Columbus, OH 43210; Kimmel Cancer Institute and Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 15261; and Department of Medicine, Helsinki University Central Hospital, and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Strout","sequence":"additional","affiliation":[{"name":"The Division of Hematology and Oncology, Department of Internal Medicine, The Comprehensive Cancer Center, and The Division of Human Cancer Genetics, Department of Molecular Virology, Immunology, and Medical Genetics, and Department of Pathology, The Ohio State University College of Medicine and Public Health, Columbus, OH 43210; Kimmel Cancer Institute and Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 15261; and Department of Medicine, Helsinki University Central Hospital, and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Becknell","sequence":"additional","affiliation":[{"name":"The Division of Hematology and Oncology, Department of Internal Medicine, The Comprehensive Cancer Center, and The Division of Human Cancer Genetics, Department of Molecular Virology, Immunology, and Medical Genetics, and Department of Pathology, The Ohio State University College of Medicine and Public Health, Columbus, OH 43210; 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Kimmel Cancer Institute and Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 15261; and Department of Medicine, Helsinki University Central Hospital, and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl S.","family":"Theil","sequence":"additional","affiliation":[{"name":"The Division of Hematology and Oncology, Department of Internal Medicine, The Comprehensive Cancer Center, and The Division of Human Cancer Genetics, Department of Molecular Virology, Immunology, and Medical Genetics, and Department of Pathology, The Ohio State University College of Medicine and Public Health, Columbus, OH 43210; Kimmel Cancer Institute and Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 15261; and Department of Medicine, Helsinki University Central Hospital, and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Krahe","sequence":"additional","affiliation":[{"name":"The Division of Hematology and Oncology, Department of Internal Medicine, The Comprehensive Cancer Center, and The Division of Human Cancer Genetics, Department of Molecular Virology, Immunology, and Medical Genetics, and Department of Pathology, The Ohio State University College of Medicine and Public Health, Columbus, OH 43210; 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