{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:28:09Z","timestamp":1781105289812,"version":"3.54.1"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,4,2]]},"abstract":"<jats:p>\n                    We used panhandle PCR to clone the der(11) genomic breakpoint junction in three leukemias with t(4;11) and devised reverse-panhandle PCR to clone the breakpoint junction of the other derivative chromosome. This work contributes two elements to knowledge on\n                    <jats:italic>MLL<\/jats:italic>\n                    translocations. First is reverse-panhandle PCR for cloning breakpoint junctions of the other derivative chromosomes, sequences of which are germane to understanding the\n                    <jats:italic>MLL<\/jats:italic>\n                    translocation process. The technique revealed duplicated sequences in one case of infant acute lymphoblastic leukemia (ALL) and small deletions in a case of treatment-related ALL. The second element is discovery of a three-way rearrangement of\n                    <jats:italic>MLL<\/jats:italic>\n                    ,\n                    <jats:italic>AF-4<\/jats:italic>\n                    , and\n                    <jats:italic>CDK6<\/jats:italic>\n                    in another case of infant ALL. Cytogenetic analysis was unsuccessful at diagnosis, but suggested t(4;11) and del(7)(q21q31) at relapse. Panhandle PCR analysis of the diagnostic marrow identified a breakpoint junction of\n                    <jats:italic>MLL<\/jats:italic>\n                    intron 8 and\n                    <jats:italic>AF-4<\/jats:italic>\n                    intron 3. Reverse-panhandle PCR identified a breakpoint junction of\n                    <jats:italic>CDK6<\/jats:italic>\n                    from band 7q21-q22 and\n                    <jats:italic>MLL<\/jats:italic>\n                    intron 9.\n                    <jats:italic>CDK6<\/jats:italic>\n                    encodes a critical cell cycle regulator and is the first gene of this type disrupted by\n                    <jats:italic>MLL<\/jats:italic>\n                    translocation. Cdk6 is overexpressed or disrupted by translocation in many cancers. The in-frame\n                    <jats:italic>CDK6-MLL<\/jats:italic>\n                    transcript is provocative with respect to a potential contribution of the predicted Cdk6-MLL fusion protein in the genesis of the ALL, which also contains an in-frame\n                    <jats:italic>MLL-AF4<\/jats:italic>\n                    transcript. The sequences in these three cases show additional\n                    <jats:italic>MLL<\/jats:italic>\n                    genomic breakpoint heterogeneity. Each breakpoint junction suggests nonhomologous end joining and is consistent with DNA damage and repair.\n                    <jats:italic>CDK6-MLL<\/jats:italic>\n                    is a new fusion of both genes.\n                  <\/jats:p>","DOI":"10.1073\/pnas.062066799","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:37:36Z","timestamp":1027679856000},"page":"4568-4573","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":45,"title":["Panhandle and reverse-panhandle PCR enable cloning of der(11) and der(other) genomic breakpoint junctions of\n                    <i>MLL<\/i>\n                    translocations and identify complex translocation of\n                    <i>MLL<\/i>\n                    ,\n                    <i>AF-4<\/i>\n                    , and\n                    <i>CDK6<\/i>"],"prefix":"10.1073","volume":"99","author":[{"given":"Leslie J.","family":"Raffini","sequence":"first","affiliation":[{"name":"Division of Oncology, Joseph Stokes, Jr. Research Institute, and Department of Human Genetics and Molecular Biology, Children's Hospital of Philadelphia, Philadelphia, PA 19104; Departments of Pediatrics and Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; and Department of Pediatrics, Memorial Sloan\u2013Kettering Cancer Center, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana J.","family":"Slater","sequence":"additional","affiliation":[{"name":"Division of Oncology, Joseph Stokes, Jr. Research Institute, and Department of Human Genetics and Molecular Biology, Children's Hospital of Philadelphia, Philadelphia, PA 19104; Departments of Pediatrics and Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; and Department of Pediatrics, Memorial Sloan\u2013Kettering Cancer Center, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric F.","family":"Rappaport","sequence":"additional","affiliation":[{"name":"Division of Oncology, Joseph Stokes, Jr. Research Institute, and Department of Human Genetics and Molecular Biology, Children's Hospital of Philadelphia, Philadelphia, PA 19104; Departments of Pediatrics and Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; and Department of Pediatrics, Memorial Sloan\u2013Kettering Cancer Center, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Lo Nigro","sequence":"additional","affiliation":[{"name":"Division of Oncology, Joseph Stokes, Jr. Research Institute, and Department of Human Genetics and Molecular Biology, Children's Hospital of Philadelphia, Philadelphia, PA 19104; Departments of Pediatrics and Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; and Department of Pediatrics, Memorial Sloan\u2013Kettering Cancer Center, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nai-Kong V.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Division of Oncology, Joseph Stokes, Jr. Research Institute, and Department of Human Genetics and Molecular Biology, Children's Hospital of Philadelphia, Philadelphia, PA 19104; 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