{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:16:47Z","timestamp":1790767007975,"version":"4.1.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2007,2,1]],"date-time":"2007-02-01T00:00:00Z","timestamp":1170288000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2007,2,1]],"date-time":"2007-02-01T00:00:00Z","timestamp":1170288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2007,4]]},"DOI":"10.1038\/sj.leu.2404563","type":"journal-article","created":{"date-parts":[[2007,2,3]],"date-time":"2007-02-03T03:46:11Z","timestamp":1170474371000},"page":"754-763","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Ectopic retroviral expression of LMO2, but not IL2R\u03b3, blocks human T-cell development from CD34+ cells: implications for leukemogenesis in gene therapy"],"prefix":"10.1038","volume":"21","author":[{"given":"K","family":"Pike-Overzet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"de Ridder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Weerkamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M R M","family":"Baert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M M A","family":"Verstegen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M H","family":"Brugman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S J","family":"Howe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M J T","family":"Reinders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A J","family":"Thrasher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Wagemaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J J M","family":"van Dongen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F J T","family":"Staal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2007,2,1]]},"reference":[{"key":"BF2404563_CR1","doi-asserted-by":"publisher","first-page":"2181","DOI":"10.1016\/S0140-6736(04)17590-9","volume":"364","author":"HB Gaspar","year":"2004","unstructured":"Gaspar HB, Parsley KL, Howe S, King D, Gilmour KC, Sinclair J et al. Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gamma retroviral vector. Lancet 2004; 364: 2181\u20132187.","journal-title":"Lancet"},{"key":"BF2404563_CR2","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/BF02982686","volume":"76","author":"S Hacein-Bey-Abina","year":"2002","unstructured":"Hacein-Bey-Abina S, Fischer A, Cavazzana-Calvo M . Gene therapy of X-linked severe combined immunodeficiency. Int J Hematol 2002; 76: 295\u2013298.","journal-title":"Int J Hematol"},{"key":"BF2404563_CR3","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1056\/NEJMoa012616","volume":"346","author":"S Hacein-Bey-Abina","year":"2002","unstructured":"Hacein-Bey-Abina S, Le Deist F, Carlier F, Bouneaud C, Hue C, De Villartay JP et al. Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. N Engl J Med 2002; 346: 1185\u20131193.","journal-title":"N Engl J Med"},{"key":"BF2404563_CR4","doi-asserted-by":"publisher","first-page":"2410","DOI":"10.1126\/science.1070104","volume":"296","author":"A Aiuti","year":"2002","unstructured":"Aiuti A, Slavin S, Aker M, Ficara F, Deola S, Mortellaro A et al. Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Science 2002; 296: 2410\u20132413.","journal-title":"Science"},{"key":"BF2404563_CR5","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1056\/NEJM200301163480314","volume":"348","author":"S Hacein-Bey-Abina","year":"2003","unstructured":"Hacein-Bey-Abina S, von Kalle C, Schmidt M, Le Deist F, Wulffraat N, McIntyre E et al. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med 2003; 348: 255\u2013256.","journal-title":"N Engl J Med"},{"key":"BF2404563_CR6","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1126\/science.299.5605.320","volume":"299","author":"E Marshall","year":"2003","unstructured":"Marshall E . Gene therapy. Second child in French trial is found to have leukemia. Science 2003; 299: 320.","journal-title":"Science"},{"key":"BF2404563_CR7","first-page":"561","volume":"433","author":"E Check","year":"2005","unstructured":"Check E . Gene therapy put on hold as third child develops cancer. Nature 2005; 433: 561.","journal-title":"Nature"},{"key":"BF2404563_CR8","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1126\/science.1088547","volume":"302","author":"S Hacein-Bey-Abina","year":"2003","unstructured":"Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 2003; 302: 415\u2013419.","journal-title":"Science"},{"key":"BF2404563_CR9","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1126\/science.1091667","volume":"303","author":"UP Dave","year":"2004","unstructured":"Dave UP, Jenkins NA, Copeland NG . Gene therapy insertional mutagenesis insights. Science 2004; 303: 333.","journal-title":"Science"},{"key":"BF2404563_CR10","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1038\/4401123a","volume":"440","author":"NB Woods","year":"2006","unstructured":"Woods NB, Bottero V, Schmidt M, von Kalle C, Verma IM . Gene therapy: therapeutic gene causing lymphoma. Nature 2006; 440: 1123.","journal-title":"Nature"},{"key":"BF2404563_CR11","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/0165-4608(92)90378-L","volume":"61","author":"AB Foot","year":"1992","unstructured":"Foot AB, Oakhill A, Kitchen C . Acute monoblastic leukemia of infancy in Klinefelter's syndrome. Cancer Genet Cytogenet 1992; 61: 99\u2013100.","journal-title":"Cancer Genet Cytogenet"},{"key":"BF2404563_CR12","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/nature01572","volume":"423","author":"J Lessard","year":"2003","unstructured":"Lessard J, Sauvageau G . Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature 2003; 423: 255\u2013260.","journal-title":"Nature"},{"key":"BF2404563_CR13","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1182\/blood.V94.6.2072","volume":"94","author":"DJ Hussey","year":"1999","unstructured":"Hussey DJ, Nicola M, Moore S, Peters GB, Dobrovic A . The (4;11)(q21;p15) translocation fuses the NUP98 and RAP1GDS1 genes and is recurrent in T-cell acute lymphocytic leukemia. Blood 1999; 94: 2072\u20132079.","journal-title":"Blood"},{"key":"BF2404563_CR14","doi-asserted-by":"publisher","first-page":"E6","DOI":"10.1038\/nature05220","volume":"443","author":"NB Woods","year":"2006","unstructured":"Woods NB, Bottero V, Schmidt M, von Kalle C, Verma IM . Gene therapy: is IL2RG oncogenic in T-cell development?: X-SCID transgene leukaemogenicity (reply). Nature 2006; 443: E6\u2013E7.","journal-title":"Nature"},{"key":"BF2404563_CR15","doi-asserted-by":"publisher","first-page":"11730","DOI":"10.1073\/pnas.0603635103","volume":"103","author":"Y Shou","year":"2006","unstructured":"Shou Y, Ma Z, Lu T, Sorrentino BP . Unique risk factors for insertional mutagenesis in a mouse model of XSCID gene therapy. Proc Natl Acad Sci USA 2006; 103: 11730\u201311735.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BF2404563_CR16","doi-asserted-by":"publisher","first-page":"E6","DOI":"10.1038\/nature05218","volume":"443","author":"K Pike-Overzet","year":"2006","unstructured":"Pike-Overzet K, de Ridder D, Weerkamp F, Baert MR, Verstegen MM, Brugman MH et al. Gene therapy: is IL2RG oncogenic in T-cell development? Nature 2006; 443: E6\u2013E7, (E5 discussion).","journal-title":"Nature"},{"key":"BF2404563_CR17","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1084\/jem.20042524","volume":"201","author":"WA Dik","year":"2005","unstructured":"Dik WA, Pike-Overzet K, Weerkamp F, de Ridder D, de Haas EF, Baert MR et al. New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling. J Exp Med 2005; 201: 1715\u20131723.","journal-title":"J Exp Med"},{"key":"BF2404563_CR18","doi-asserted-by":"crossref","first-page":"4013","DOI":"10.1182\/blood.V92.11.4013.423k53_4013_4022","volume":"92","author":"PB van Hennik","year":"1998","unstructured":"van Hennik PB, Verstegen MM, Bierhuizen MF, Limon A, Wognum AW, Cancelas JA et al. Highly efficient transduction of the green fluorescent protein gene in human umbilical cord blood stem cells capable of cobblestone formation in long-term cultures and multilineage engraftment of immunodeficient mice. Blood 1998; 92: 4013\u20134022.","journal-title":"Blood"},{"key":"BF2404563_CR19","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1089\/104303400750001435","volume":"11","author":"AW Wognum","year":"2000","unstructured":"Wognum AW, Visser TP, Peters K, Bierhuizen MF, Wagemaker G . Stimulation of mouse bone marrow cells with kit ligand, FLT3 ligand, and thrombopoietin leads to efficient retrovirus-mediated gene transfer to stem cells, whereas interleukin 3 and interleukin 11 reduce transduction of short- and long-term repopulating cells. Hum Gene Ther 2000; 11: 2129\u20132141.","journal-title":"Hum Gene Ther"},{"key":"BF2404563_CR20","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1126\/science.288.5466.669","volume":"288","author":"M Cavazzana-Calvo","year":"2000","unstructured":"Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, Gross F, Yvon E, Nusbaum P et al. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 2000; 288: 669\u2013672.","journal-title":"Science"},{"key":"BF2404563_CR21","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1093\/biostatistics\/4.2.249","volume":"4","author":"RA Irizarry","year":"2003","unstructured":"Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U et al. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 2003; 4: 249\u2013264.","journal-title":"Biostatistics"},{"key":"BF2404563_CR22","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1093\/bioinformatics\/19.2.185","volume":"19","author":"BM Bolstad","year":"2003","unstructured":"Bolstad BM, Irizarry RA, Astrand M, Speed TP . A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 2003; 19: 185\u2013193.","journal-title":"Bioinformatics"},{"key":"BF2404563_CR23","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1093\/bioinformatics\/bti788","volume":"22","author":"D de Ridder","year":"2006","unstructured":"de Ridder D, Staal FJ, van Dongen JJ, Reinders MJ . Maximum significance clustering of oligonucleotide microarrays. Bioinformatics 2006; 22: 326\u2013331.","journal-title":"Bioinformatics"},{"key":"BF2404563_CR24","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1089\/hum.1996.7.12-1405","volume":"7","author":"TM Kinsella","year":"1996","unstructured":"Kinsella TM, Nolan GP . Episomal vectors rapidly and stably produce high-titer recombinant retrovirus. Hum Gene Ther 1996; 7: 1405\u20131413.","journal-title":"Hum Gene Ther"},{"key":"BF2404563_CR25","doi-asserted-by":"publisher","first-page":"3131","DOI":"10.1182\/blood-2005-08-3412","volume":"107","author":"F Weerkamp","year":"2006","unstructured":"Weerkamp F, Baert MR, Brugman MH, Dik WA, de Haas EF, Visser TP et al. Human thymus contains multipotent progenitors with T\/B lymphoid, myeloid, and erythroid lineage potential. Blood 2006; 107: 3131\u20133137.","journal-title":"Blood"},{"key":"BF2404563_CR26","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/S0092-8674(02)00864-4","volume":"110","author":"AR Schroder","year":"2002","unstructured":"Schroder AR, Shinn P, Chen H, Berry C, Ecker JR, Bushman F . HIV-1 integration in the human genome favors active genes and local hotspots. Cell 2002; 110: 521\u2013529.","journal-title":"Cell"},{"key":"BF2404563_CR27","doi-asserted-by":"publisher","first-page":"E234","DOI":"10.1371\/journal.pbio.0020234","volume":"2","author":"RS Mitchell","year":"2004","unstructured":"Mitchell RS, Beitzel BF, Schroder AR, Shinn P, Chen H, Berry CC et al. Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences. PLoS Biol 2004; 2: E234.","journal-title":"PLoS Biol"},{"key":"BF2404563_CR28","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1189\/jlb.0603287","volume":"75","author":"YY Ng","year":"2004","unstructured":"Ng YY, van Kessel B, Lakhorst HM, Baert MR, van den Burg CM, Bloem AC et al. Gene expression profiling of CD34+ cells from various hematopoietic stem-cell sources reveals functional differences in stem-cell activity. J Leukoc Biol 2004; 75: 314\u2013323.","journal-title":"J Leukoc Biol"},{"key":"BF2404563_CR29","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1111\/j.1600-065X.1998.tb01231.x","volume":"165","author":"H Spits","year":"1998","unstructured":"Spits H, Blom B, Jaleco AC, Weijer K, Verschuren MC, van Dongen JJ et al. Early stages in the development of human T, natural killer and thymic dendritic cells. Immunol Rev 1998; 165: 75\u201386.","journal-title":"Immunol Rev"},{"key":"BF2404563_CR30","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1016\/j.jaci.2004.10.031","volume":"115","author":"F Weerkamp","year":"2005","unstructured":"Weerkamp F, de Haas EF, Naber BA, Comans-Bitter WM, Bogers AJ, van Dongen JJ et al. Age-related changes in the cellular composition of the thymus in children. J Allergy Clin Immunol 2005; 115: 834\u2013840.","journal-title":"J Allergy Clin Immunol"},{"key":"BF2404563_CR31","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1038\/3877","volume":"20","author":"A Puel","year":"1998","unstructured":"Puel A, Ziegler SF, Buckley RH, Leonard WJ . Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency. Nat Genet 1998; 20: 394\u2013397.","journal-title":"Nat Genet"},{"key":"BF2404563_CR32","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1182\/blood.V96.8.2803","volume":"96","author":"CM Roifman","year":"2000","unstructured":"Roifman CM, Zhang J, Chitayat D, Sharfe N . A partial deficiency of interleukin-7R alpha is sufficient to abrogate T-cell development and cause severe combined immunodeficiency. Blood 2000; 96: 2803\u20132807.","journal-title":"Blood"},{"key":"BF2404563_CR33","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1126\/science.1068893","volume":"296","author":"Z Li","year":"2002","unstructured":"Li Z, Dullmann J, Schiedlmeier B, Schmidt M, von Kalle C, Meyer J et al. Murine leukemia induced by retroviral gene marking. Science 2002; 296: 497.","journal-title":"Science"},{"key":"BF2404563_CR34","doi-asserted-by":"publisher","first-page":"2530","DOI":"10.1182\/blood-2005-03-1115","volume":"106","author":"B Calmels","year":"2005","unstructured":"Calmels B, Ferguson C, Laukkanen MO, Adler R, Faulhaber M, Kim HJ et al. Recurrent retroviral vector integration at the Mds1\/Evi1 locus in nonhuman primate hematopoietic cells. Blood 2005; 106: 2530\u20132533.","journal-title":"Blood"},{"key":"BF2404563_CR35","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.it.2006.01.006","volume":"27","author":"F Weerkamp","year":"2006","unstructured":"Weerkamp F, Pike-Overzet K, Staal FJ . T-sing progenitors to commit. Trends Immunol 2006; 27: 125\u2013131.","journal-title":"Trends Immunol"},{"key":"BF2404563_CR36","doi-asserted-by":"publisher","first-page":"E5","DOI":"10.1038\/nature05219","volume":"443","author":"AJ Thrasher","year":"2006","unstructured":"Thrasher AJ, Gaspar HB, Baum C, Modlich U, Schambach A, Candotti F et al. Gene therapy: X-SCID transgene leukaemogenicity. Nature 2006; 443: E5\u2013E6, (discussion E6\u2013E7).","journal-title":"Nature"},{"key":"BF2404563_CR37","first-page":"853","volume":"11","author":"RC Larson","year":"1995","unstructured":"Larson RC, Osada H, Larson TA, Lavenir I, Rabbitts TH . The oncogenic LIM protein Rbtn2 causes thymic developmental aberrations that precede malignancy in transgenic mice. Oncogene 1995; 11: 853\u2013862.","journal-title":"Oncogene"},{"key":"BF2404563_CR38","doi-asserted-by":"crossref","first-page":"3060","DOI":"10.1182\/blood.V86.8.3060.3060","volume":"86","author":"GA Neale","year":"1995","unstructured":"Neale GA, Rehg JE, Goorha RM . Ectopic expression of rhombotin-2 causes selective expansion of CD4-CD8- lymphocytes in the thymus and T-cell tumors in transgenic mice. Blood 1995; 86: 3060\u20133071.","journal-title":"Blood"},{"key":"BF2404563_CR39","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1038\/ni878","volume":"4","author":"D Allman","year":"2003","unstructured":"Allman D, Sambandam A, Kim S, Miller JP, Pagan A, Well D et al. Thymopoiesis independent of common lymphoid progenitors. Nat Immunol 2003; 4: 168\u2013174.","journal-title":"Nat Immunol"},{"key":"BF2404563_CR40","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1126\/science.1102160","volume":"306","author":"AP Weng","year":"2004","unstructured":"Weng AP, Ferrando AA, Lee W, Morris JPt, Silverman LB, Sanchez-Irizarry C et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 2004; 306: 269\u2013271.","journal-title":"Science"},{"key":"BF2404563_CR41","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1126\/science.1086238","volume":"300","author":"D Trono","year":"2003","unstructured":"Trono D . Virology. Picking the right spot. Science 2003; 300: 1670\u20131671.","journal-title":"Science"},{"key":"BF2404563_CR42","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.ymthe.2003.10.013","volume":"9","author":"C Baum","year":"2004","unstructured":"Baum C, von Kalle C, Staal FJ, Li Z, Fehse B, Schmidt M et al. Chance or necessity? Insertional mutagenesis in gene therapy and its consequences. Mol Ther 2004; 9: 5\u201313.","journal-title":"Mol Ther"}],"container-title":["Leukemia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/2404563.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/2404563","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/2404563.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T02:40:51Z","timestamp":1648780851000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/2404563"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,2,1]]},"references-count":42,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2007,4]]}},"alternative-id":["BF2404563"],"URL":"https:\/\/doi.org\/10.1038\/sj.leu.2404563","relation":{},"ISSN":["0887-6924","1476-5551"],"issn-type":[{"value":"0887-6924","type":"print"},{"value":"1476-5551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,2,1]]},"assertion":[{"value":"29 November 2006","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 December 2006","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 February 2007","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}