{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:44:21Z","timestamp":1781109861488,"version":"3.54.1"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,11,12]]},"abstract":"<jats:p>\n                    The t(1;19) translocation yields a fusion between\n                    <jats:italic>E2A<\/jats:italic>\n                    and\n                    <jats:italic>PBX1<\/jats:italic>\n                    genes and occurs in 5% of acute lymphoblastic leukemia in children and adults. We used chromosomal translocations and Ig heavy chain (\n                    <jats:italic>IGH<\/jats:italic>\n                    )\/T cell antigen receptor (\n                    <jats:italic>TCR<\/jats:italic>\n                    ) rearrangements to develop an understanding of the etiology and natural history of this subtype of leukemia. We sequenced the genomic fusion between\n                    <jats:italic>E2A<\/jats:italic>\n                    and\n                    <jats:italic>PBX1<\/jats:italic>\n                    in 22 preB acute lymphoblastic leukemias and two cell lines. The prenatal origin of the leukemia was assessed in 15 pediatric patients by screening for the clonotypic\n                    <jats:italic>E2A<\/jats:italic>\n                    -\n                    <jats:italic>PBX1<\/jats:italic>\n                    translocation in neonatal blood spots, or Guthrie cards, obtained from the children at the time of birth. Two patients were determined to be weakly positive for the fusion at the time of birth, in contrast to previously studied childhood leukemia fusions, t(12;21), t(8;21), and t(4;11), which were predominantly prenatal. The presence of extensive\n                    <jats:italic>N<\/jats:italic>\n                    -nucleotides at the point of fusion in the\n                    <jats:italic>E2A<\/jats:italic>\n                    -\n                    <jats:italic>PBX1<\/jats:italic>\n                    translocation as well as specific characteristics of the\n                    <jats:italic>IGH<\/jats:italic>\n                    \/\n                    <jats:italic>TCR<\/jats:italic>\n                    rearrangements provided additional evidence for a postnatal, preB cell origin. Intriguingly, 16 of 24 breakpoints on the 3.2-kb\n                    <jats:italic>E2A<\/jats:italic>\n                    intron 14 were located within 5 bp, providing evidence for a site-specific recombination mechanism. Breakpoints on the 232-kb\n                    <jats:italic>PBX1<\/jats:italic>\n                    intron 1 were more dispersed but highly clustered proximal to exon 2. In sum, the translocation breakpoints displayed evidence of unique temporal, ontological, and mechanistic formation than the previously analyzed pediatric leukemia translocation breakpoints and emphasize the need to differentiate cytogenetic and molecular subgroups for studies of leukemia causality.\n                  <\/jats:p>","DOI":"10.1073\/pnas.222481199","type":"journal-article","created":{"date-parts":[[2002,11,12]],"date-time":"2002-11-12T13:44:20Z","timestamp":1037108660000},"page":"15101-15106","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":103,"title":["Site-specific translocation and evidence of postnatal origin of the t(1;19)\n                    <i>E2A-PBX1<\/i>\n                    fusion in childhood acute lymphoblastic leukemia"],"prefix":"10.1073","volume":"99","author":[{"given":"Joseph L.","family":"Wiemels","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143; School of Public Health, University of California, Berkeley, CA 94720; Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32611; Valley Children's Hospital, 9300 Valley Children's Place, FC13, Madera, CA 93638; and Children's Cancer Research Laboratory, Basic Science Building Room 401, New York Medical College, Valhalla, NY 10595"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C.","family":"Leonard","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143; School of Public Health, University of California, Berkeley, CA 94720; Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32611; Valley Children's Hospital, 9300 Valley Children's Place, FC13, Madera, CA 93638; and Children's Cancer Research Laboratory, Basic Science Building Room 401, New York Medical College, Valhalla, NY 10595"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143; School of Public Health, University of California, Berkeley, CA 94720; Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32611; Valley Children's Hospital, 9300 Valley Children's Place, FC13, Madera, CA 93638; and Children's Cancer Research Laboratory, Basic Science Building Room 401, New York Medical College, Valhalla, NY 10595"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Segal","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143; School of Public Health, University of California, Berkeley, CA 94720; Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32611; Valley Children's Hospital, 9300 Valley Children's Place, FC13, Madera, CA 93638; and Children's Cancer Research Laboratory, Basic Science Building Room 401, New York Medical College, Valhalla, NY 10595"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Hunger","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143; School of Public Health, University of California, Berkeley, CA 94720; Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32611; Valley Children's Hospital, 9300 Valley Children's Place, FC13, Madera, CA 93638; and Children's Cancer Research Laboratory, Basic Science Building Room 401, New York Medical College, Valhalla, NY 10595"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martyn T.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143; School of Public Health, University of California, Berkeley, CA 94720; Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32611; Valley Children's Hospital, 9300 Valley Children's Place, FC13, Madera, CA 93638; and Children's Cancer Research Laboratory, Basic Science Building Room 401, New York Medical College, Valhalla, NY 10595"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vonda","family":"Crouse","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143; School of Public Health, University of California, Berkeley, CA 94720; Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32611; Valley Children's Hospital, 9300 Valley Children's Place, FC13, Madera, CA 93638; and Children's Cancer Research Laboratory, Basic Science Building Room 401, New York Medical College, Valhalla, NY 10595"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143; School of Public Health, University of California, Berkeley, CA 94720; Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32611; Valley Children's Hospital, 9300 Valley Children's Place, FC13, Madera, CA 93638; and Children's Cancer Research Laboratory, Basic Science Building Room 401, New York Medical College, Valhalla, NY 10595"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia A.","family":"Buffler","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143; School of Public Health, University of California, Berkeley, CA 94720; Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32611; Valley Children's Hospital, 9300 Valley Children's Place, FC13, Madera, CA 93638; and Children's Cancer Research Laboratory, Basic Science Building Room 401, New York Medical College, Valhalla, NY 10595"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon R.","family":"Pine","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143; School of Public Health, University of California, Berkeley, CA 94720; Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32611; Valley Children's Hospital, 9300 Valley Children's Place, FC13, Madera, CA 93638; and Children's Cancer Research Laboratory, Basic Science Building Room 401, New York Medical College, Valhalla, NY 10595"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,11]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.070061297"},{"key":"e_1_3_3_2_2","first-page":"2542","volume":"61","author":"Alexander F. 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