{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:38:52Z","timestamp":1787067532210,"version":"build-2736575974"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2023,8,26]],"date-time":"2023-08-26T00:00:00Z","timestamp":1693008000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,8,26]],"date-time":"2023-08-26T00:00:00Z","timestamp":1693008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000050","name":"U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R35HL135795"],"award-info":[{"award-number":["R35HL135795"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Complete or partial deletions of chromosome 7 (-7\/del7q) belong to the most frequent chromosomal abnormalities in myeloid neoplasm (MN) and are associated with a poor prognosis. The disease biology of -7\/del7q and the genes responsible for the leukemogenic properties have not been completely elucidated. Chromosomal deletions may create clonal vulnerabilities due to haploinsufficient (HI) genes contained in the deleted regions. Therefore, HI genes are potential targets of synthetic lethal strategies. Through the most comprehensive multimodal analysis of more than 600 -7\/del7q MN samples, we elucidated the disease biology and qualified a list of most consistently deleted and HI genes. Among them, 27 potentially synthetic lethal target genes were identified with the following properties: (i) unaffected genes by hemizygous\/homozygous LOF mutations; (ii) prenatal lethality in knockout mice; and (iii) vulnerability of leukemia cells by CRISPR and shRNA knockout screens. In -7\/del7q cells, we also identified 26 up or down-regulated genes mapping on other chromosomes as downstream pathways or compensation mechanisms. Our findings shed light on the pathogenesis of -7\/del7q MNs, while 27 potential synthetic lethal target genes and 26 differential expressed genes allow for a therapeutic window of -7\/del7q.<\/jats:p>","DOI":"10.1038\/s41375-023-02003-x","type":"journal-article","created":{"date-parts":[[2023,8,26]],"date-time":"2023-08-26T04:03:15Z","timestamp":1693022595000},"page":"2082-2093","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Genomics of deletion 7 and 7q in myeloid neoplasm: from pathogenic culprits to potential synthetic lethal therapeutic targets"],"prefix":"10.1038","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4274-8714","authenticated-orcid":false,"given":"Minako","family":"Mori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7909-5422","authenticated-orcid":false,"given":"Yasuo","family":"Kubota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8394-600X","authenticated-orcid":false,"given":"Arda","family":"Durmaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelo","family":"Gurnari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charnise","family":"Goodings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Adema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0157-7720","authenticated-orcid":false,"given":"Ben","family":"Ponvilawan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waled S.","family":"Bahaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tariq","family":"Kewan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"LaFramboise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manja","family":"Meggendorfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6333-5049","authenticated-orcid":false,"given":"Claudia","family":"Haferlach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2403-8268","authenticated-orcid":false,"given":"John","family":"Barnard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Wlodarski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2993-1509","authenticated-orcid":false,"given":"Valeria","family":"Visconte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0196-2837","authenticated-orcid":false,"given":"Torsten","family":"Haferlach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6837-4346","authenticated-orcid":false,"given":"Jaroslaw P.","family":"Maciejewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,26]]},"reference":[{"key":"2003_CR1","doi-asserted-by":"publisher","first-page":"4385","DOI":"10.1182\/blood-2007-03-082404","volume":"110","author":"D Haase","year":"2007","unstructured":"Haase D, Germing U, Schanz J, Pfeilst\u00f6cker M, N\u00f6sslinger T, Hildebrandt B, et al. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood. 2007;110:4385\u201395.","journal-title":"Blood."},{"key":"2003_CR2","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1002\/ajh.23230","volume":"87","author":"FT Hussain","year":"2012","unstructured":"Hussain FT, Nguyen EP, Raza S, Knudson R, Pardanani A, Hanson CA, et al. Sole abnormalities of chromosome 7 in myeloid malignancies: spectrum, histopathologic correlates, and prognostic implications. Am J Hematol. 2012;87:684\u20136.","journal-title":"Am J Hematol"},{"key":"2003_CR3","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1038\/nrc.2017.60","volume":"17","author":"ME McNerney","year":"2017","unstructured":"McNerney ME, Godley LA, Le Beau MM. Therapy-related myeloid neoplasms: when genetics and environment collide. Nat Rev Cancer. 2017;17:513\u201327.","journal-title":"Nat Rev Cancer"},{"key":"2003_CR4","doi-asserted-by":"publisher","first-page":"2454","DOI":"10.1182\/blood-2012-03-420489","volume":"120","author":"PL Greenberg","year":"2012","unstructured":"Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Sol\u00e9 F, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120:2454\u201365.","journal-title":"Blood."},{"key":"2003_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01590-5","volume":"8","author":"JR Schwartz","year":"2017","unstructured":"Schwartz JR, Ma J, Lamprecht T, Walsh M, Wang S, Bryant V, et al. The genomic landscape of pediatric myelodysplastic syndromes. Nat Commun. 2017;8:1557.","journal-title":"Nat Commun"},{"key":"2003_CR6","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1016\/j.hoc.2018.04.007","volume":"32","author":"MW Wlodarski","year":"2018","unstructured":"Wlodarski MW, Sahoo SS, Niemeyer CM. Monosomy 7 in pediatric myelodysplastic syndromes. Hematol Oncol Clin North Am. 2018;32:729\u201343.","journal-title":"Hematol Oncol Clin North Am"},{"key":"2003_CR7","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1038\/leu.2014.25","volume":"28","author":"N Hosono","year":"2014","unstructured":"Hosono N, Makishima H, Jerez A, Yoshida K, Przychodzen B, McMahon S, et al. Recurrent genetic defects on chromosome 7q in myeloid neoplasms. Leukemia. 2014;28:1348\u201351.","journal-title":"Leukemia."},{"key":"2003_CR8","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1182\/asheducation-2011.1.90","volume":"2011","author":"MG Afable","year":"2011","unstructured":"Afable MG, Tiu RV, Maciejewski JP. Clonal evolution in aplastic anemia. Hematol Am Soc Hematol Educ Program. 2011;2011:90\u20135.","journal-title":"Hematol Am Soc Hematol Educ Program"},{"key":"2003_CR9","doi-asserted-by":"publisher","first-page":"2891","DOI":"10.1182\/blood-2017-12-822262","volume":"131","author":"T Inaba","year":"2018","unstructured":"Inaba T, Honda H, Matsui H. The enigma of monosomy 7. Blood. 2018;131:2891\u20138.","journal-title":"Blood."},{"key":"2003_CR10","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1038\/nbt.3178","volume":"33","author":"AG Kotini","year":"2015","unstructured":"Kotini AG, Chang CJ, Boussaad I, Delrow JJ, Dolezal EK, Nagulapally AB, et al. Functional analysis of a chromosomal deletion associated with myelodysplastic syndromes using isogenic human induced pluripotent stem cells. Nat Biotechnol. 2015;33:646\u201355.","journal-title":"Nat Biotechnol"},{"key":"2003_CR11","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1038\/s41375-021-01491-z","volume":"36","author":"JT Baeten","year":"2022","unstructured":"Baeten JT, Liu W, Preddy IC, Zhou N, McNerney ME. CRISPR screening in human hematopoietic stem and progenitor cells reveals an enrichment for tumor suppressor genes within chromosome 7 commonly deleted regions. Leukemia. 2022;36:1421\u20135.","journal-title":"Leukemia."},{"key":"2003_CR12","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1038\/ng.621","volume":"42","author":"T Ernst","year":"2010","unstructured":"Ernst T, Chase AJ, Score J, Hidalgo-Curtis CE, Bryant C, Jones AV, et al. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet. 2010;42:722\u20136.","journal-title":"Nat Genet"},{"key":"2003_CR13","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.1038\/leu.2010.167","volume":"24","author":"H Makishima","year":"2010","unstructured":"Makishima H, Jankowska AM, Tiu RV, Szpurka H, Sugimoto Y, Hu Z, et al. Novel homo- and hemizygous mutations in EZH2 in myeloid malignancies. Leukemia. 2010;24:1799\u2013804.","journal-title":"Leukemia."},{"key":"2003_CR14","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.ccr.2013.08.011","volume":"24","author":"A Nagamachi","year":"2013","unstructured":"Nagamachi A, Matsui H, Asou H, Ozaki Y, Aki D, Kanai A, et al. Haploinsufficiency of SAMD9L, an endosome fusion facilitator, causes myeloid malignancies in mice mimicking human diseases with monosomy 7. Cancer Cell. 2013;24:305\u201317.","journal-title":"Cancer Cell"},{"key":"2003_CR15","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1038\/ng.620","volume":"42","author":"G Nikoloski","year":"2010","unstructured":"Nikoloski G, Langemeijer SM, Kuiper RP, Knops R, Massop M, T\u00f6nnissen ER, et al. Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes. Nat Genet. 2010;42:665\u20137.","journal-title":"Nat Genet"},{"key":"2003_CR16","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1038\/s41591-021-01511-6","volume":"27","author":"SS Sahoo","year":"2021","unstructured":"Sahoo SS, Pastor VB, Goodings C, Voss RK, Kozyra EJ, Szvetnik A, et al. Clinical evolution, genetic landscape and trajectories of clonal hematopoiesis in SAMD9\/SAMD9L syndromes. Nat Med. 2021;27:1806\u201317.","journal-title":"Nat Med"},{"key":"2003_CR17","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1038\/nrg.2017.47","volume":"18","author":"NJ O\u2019Neil","year":"2017","unstructured":"O\u2019Neil NJ, Bailey ML, Hieter P. Synthetic lethality and cancer. Nat Rev Genet. 2017;18:613\u201323.","journal-title":"Nat Rev Genet"},{"key":"2003_CR18","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1016\/j.ccell.2017.11.003","volume":"32","author":"R Pan","year":"2017","unstructured":"Pan R, Ruvolo V, Mu H, Leverson JD, Nichols G, Reed JC, et al. Synthetic lethality of combined Bcl-2 inhibition and p53 activation in AML: mechanisms and superior antileukemic efficacy. Cancer Cell. 2017;32:748\u201360.e6.","journal-title":"Cancer Cell"},{"key":"2003_CR19","doi-asserted-by":"publisher","first-page":"2059","DOI":"10.1056\/NEJMoa1301689","volume":"368","author":"TJ Ley","year":"2013","unstructured":"Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ, Robertson A, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368:2059\u201374.","journal-title":"N Engl J Med"},{"key":"2003_CR20","doi-asserted-by":"publisher","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","volume":"374","author":"E Papaemmanuil","year":"2016","unstructured":"Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374:2209\u201321.","journal-title":"N Engl J Med"},{"key":"2003_CR21","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1038\/s41586-018-0623-z","volume":"562","author":"JW Tyner","year":"2018","unstructured":"Tyner JW, Tognon CE, Bottomly D, Wilmot B, Kurtz SE, Savage SL, et al. Functional genomic landscape of acute myeloid leukaemia. Nature. 2018;562:526\u201331.","journal-title":"Nature."},{"key":"2003_CR22","doi-asserted-by":"publisher","first-page":"104059","DOI":"10.1016\/j.ebiom.2022.104059","volume":"80","author":"V Adema","year":"2022","unstructured":"Adema V, Palomo L, Walter W, Mallo M, Hutter S, La Framboise T, et al. Pathophysiologic and clinical implications of molecular profiles resultant from deletion 5q. EBioMedicine. 2022;80:104059.","journal-title":"EBioMedicine."},{"key":"2003_CR23","doi-asserted-by":"publisher","first-page":"6109","DOI":"10.1182\/blood-2011-12-397620","volume":"119","author":"A Jerez","year":"2012","unstructured":"Jerez A, Sugimoto Y, Makishima H, Verma A, Jankowska AM, Przychodzen B, et al. Loss of heterozygosity in 7q myeloid disorders: clinical associations and genomic pathogenesis. Blood. 2012;119:6109\u201317.","journal-title":"Blood."},{"key":"2003_CR24","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.1182\/blood.2020010603","volume":"138","author":"H Awada","year":"2021","unstructured":"Awada H, Durmaz A, Gurnari C, Kishtagari A, Meggendorfer M, Kerr CM, et al. Machine learning integrates genomic signatures for subclassification beyond primary and secondary acute myeloid leukemia. Blood. 2021;138:1885\u201395.","journal-title":"Blood."},{"key":"2003_CR25","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.3324\/haematol.2017.166173","volume":"102","author":"M Meggendorfer","year":"2017","unstructured":"Meggendorfer M, Haferlach C, Kern W, Haferlach T. Molecular analysis of myelodysplastic syndrome with isolated deletion of the long arm of chromosome 5 reveals a specific spectrum of molecular mutations with prognostic impact: a study on 123 patients and 27 genes. Haematologica. 2017;102:1502\u201310.","journal-title":"Haematologica."},{"key":"2003_CR26","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1038\/s41375-018-0026-z","volume":"32","author":"M Meggendorfer","year":"2018","unstructured":"Meggendorfer M, Cappelli LV, Walter W, Haferlach C, Kern W, Falini B, et al. IDH1R132, IDH2R140 and IDH2R172 in AML: different genetic landscapes correlate with outcome and may influence targeted treatment strategies. Leukemia. 2018;32:1249\u201353.","journal-title":"Leukemia."},{"key":"2003_CR27","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.1182\/blood.2019004229","volume":"136","author":"L Palomo","year":"2020","unstructured":"Palomo L, Meggendorfer M, Hutter S, Twardziok S, Adem\u00e0 V, Fuhrmann I, et al. Molecular landscape and clonal architecture of adult myelodysplastic\/myeloproliferative neoplasms. Blood. 2020;136:1851\u201362.","journal-title":"Blood."},{"key":"2003_CR28","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.1038\/s41375-022-01729-4","volume":"36","author":"Y Kubota","year":"2022","unstructured":"Kubota Y, Zawit M, Durrani J, Shen W, Bahaj WS, Kewan T, et al. Significance of hereditary gene alterations for the pathogenesis of adult bone marrow failure versus myeloid neoplasia. Leukemia. 2022;36:2827\u201334.","journal-title":"Leukemia"},{"key":"2003_CR29","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1182\/blood-2012-04-426965","volume":"121","author":"ME McNerney","year":"2013","unstructured":"McNerney ME, Brown CD, Wang X, Bartom ET, Karmakar S, Bandlamudi C, et al. CUX1 is a haploinsufficient tumor suppressor gene on chromosome 7 frequently inactivated in acute myeloid leukemia. Blood. 2013;121:975\u201383.","journal-title":"Blood."},{"key":"2003_CR30","doi-asserted-by":"publisher","first-page":"5638","DOI":"10.1158\/1078-0432.CCR-19-0924","volume":"25","author":"S Sundaravel","year":"2019","unstructured":"Sundaravel S, Kuo WL, Jeong JJ, Choudhary GS, Gordon-Mitchell S, Liu H, et al. Loss of function of DOCK4 in myelodysplastic syndromes stem cells is restored by inhibitors of DOCK4 signaling networks. Clin Cancer Res. 2019;25:5638\u201349.","journal-title":"Clin Cancer Res"},{"key":"2003_CR31","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1038\/s41586-019-1103-9","volume":"568","author":"FM Behan","year":"2019","unstructured":"Behan FM, Iorio F, Picco G, Gon\u00e7alves E, Beaver CM, Migliardi G, et al. Prioritization of cancer therapeutic targets using CRISPR-Cas9 screens. Nature. 2019;568:511\u20136.","journal-title":"Nature."},{"key":"2003_CR32","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1016\/j.cell.2017.06.010","volume":"170","author":"A Tsherniak","year":"2017","unstructured":"Tsherniak A, Vazquez F, Montgomery PG, Weir BA, Kryukov G, Cowley GS, et al. Defining a cancer dependency map. Cell. 2017;170:564\u201376.e16.","journal-title":"Cell."},{"key":"2003_CR33","doi-asserted-by":"publisher","first-page":"2441","DOI":"10.1038\/s41375-020-0728-x","volume":"34","author":"E Cris\u00e0","year":"2020","unstructured":"Cris\u00e0 E, Kulasekararaj AG, Adema V, Such E, Schanz J, Haase D, et al. Impact of somatic mutations in myelodysplastic patients with isolated partial or total loss of chromosome 7. Leukemia. 2020;34:2441\u201350.","journal-title":"Leukemia."},{"key":"2003_CR34","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.leukres.2017.01.016","volume":"55","author":"HD Gur","year":"2017","unstructured":"Gur HD, Wang SA, Tang Z, Hu S, Li S, Medeiros LJ, et al. Clinical significance of isolated del(7p) in myeloid neoplasms. Leuk Res. 2017;55:18\u201322.","journal-title":"Leuk Res"},{"key":"2003_CR35","doi-asserted-by":"publisher","first-page":"2871","DOI":"10.1182\/blood-2018-04-844746","volume":"131","author":"RK Schneider","year":"2018","unstructured":"Schneider RK, Delwel R. Puzzling pieces of chromosome 7 loss or deletion. Blood. 2018;131:2871\u20132.","journal-title":"Blood."},{"key":"2003_CR36","doi-asserted-by":"publisher","first-page":"e07839","DOI":"10.7554\/eLife.07839","volume":"4","author":"C Wong","year":"2015","unstructured":"Wong JC, Weinfurtner KM, Alzamora MEP, Kogan SC, Burgess MR, Zhang Y, et al. Functional evidence implicating chromosome 7q22 haploinsufficiency in myelodysplastic syndrome pathogenesis. eLife. 2015;4:e07839.","journal-title":"eLife"},{"key":"2003_CR37","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/nrc3805","volume":"14","author":"ZM Ramdzan","year":"2014","unstructured":"Ramdzan ZM, Nepveu A. CUX1, a haploinsufficient tumour suppressor gene overexpressed in advanced cancers. Nat Rev Cancer. 2014;14:673\u201382.","journal-title":"Nat Rev Cancer"},{"key":"2003_CR38","doi-asserted-by":"publisher","first-page":"e117","DOI":"10.1038\/bcj.2013.16","volume":"3","author":"H Singh","year":"2013","unstructured":"Singh H, Lane AA, Correll M, Przychodzen B, Sykes DB, Stone RM. et al. Putative RNA-splicing gene LUC7L2 on 7q34 represents a candidate gene in pathogenesis of myeloid malignancies. Blood Cancer J. 2013;3:e117","journal-title":"Blood Cancer J"},{"key":"2003_CR39","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1182\/blood.2021010764","volume":"138","author":"MT Voso","year":"2021","unstructured":"Voso MT, Falconi G, Fabiani E. What\u2019s new in the pathogenesis and treatment of therapy-related myeloid neoplasms. Blood. 2021;138:749\u201357.","journal-title":"Blood."},{"key":"2003_CR40","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1056\/NEJMoa2109167","volume":"386","author":"S Goyal","year":"2022","unstructured":"Goyal S, Tisdale J, Schmidt M, Kanter J, Jaroscak J, Whitney D, et al. Acute myeloid leukemia case after gene therapy for sickle cell disease. N Engl J Med. 2022;386:138\u201347.","journal-title":"N Engl J Med"},{"key":"2003_CR41","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.1182\/blood-2017-02-767731","volume":"130","author":"E Negoro","year":"2017","unstructured":"Negoro E, Nagata Y, Clemente MJ, Hosono N, Shen W, Nazha A, et al. Origins of myelodysplastic syndromes after aplastic anemia. Blood. 2017;130:1953\u20137.","journal-title":"Blood."},{"key":"2003_CR42","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1172\/JCI44111","volume":"121","author":"R Zhao","year":"2011","unstructured":"Zhao R, Yeung SC, Chen J, Iwakuma T, Su CH, Chen B, et al. Subunit 6 of the COP9 signalosome promotes tumorigenesis in mice through stabilization of MDM2 and is upregulated in human cancers. J Clin Invest. 2011;121:851\u201365.","journal-title":"J Clin Invest"},{"key":"2003_CR43","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1038\/ng725","volume":"29","author":"Z Herceg","year":"2001","unstructured":"Herceg Z, Hulla W, Gell D, Cuenin C, Lleonart M, Jackson S, et al. Disruption of Trrap causes early embryonic lethality and defects in cell cycle progression. Nat Genet. 2001;29:206\u201311.","journal-title":"Nat Genet"},{"key":"2003_CR44","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/978-981-15-1025-0_10","volume":"1217","author":"T Nakagawa","year":"2020","unstructured":"Nakagawa T, Nakayama K, Nakayama KI. Knockout mouse models provide insight into the biological functions of CRL1 components. Adv Exp Med Biol. 2020;1217:147\u201371.","journal-title":"Adv Exp Med Biol"},{"key":"2003_CR45","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.1128\/MCB.22.5.1424-1437.2002","volume":"22","author":"MX Luong","year":"2002","unstructured":"Luong MX, van der Meijden CM, Xing D, Hesselton R, Monuki ES, Jones SN, et al. Genetic ablation of the CDP\/Cux protein C terminus results in hair cycle defects and reduced male fertility. Mol Cell Biol. 2002;22:1424\u201337.","journal-title":"Mol Cell Biol"},{"key":"2003_CR46","doi-asserted-by":"publisher","first-page":"4330","DOI":"10.1128\/MCB.21.13.4330-4336.2001","volume":"21","author":"D O\u2019Carroll","year":"2001","unstructured":"O\u2019Carroll D, Erhardt S, Pagani M, Barton SC, Surani MA, Jenuwein T. The polycomb-group gene Ezh2 is required for early mouse development. Mol Cell Biol. 2001;21:4330\u20136.","journal-title":"Mol Cell Biol"},{"key":"2003_CR47","doi-asserted-by":"publisher","first-page":"2164","DOI":"10.1182\/bloodadvances.2018028423","volume":"3","author":"M Aly","year":"2019","unstructured":"Aly M, Ramdzan ZM, Nagata Y, Balasubramanian SK, Hosono N, Makishima H, et al. Distinct clinical and biological implications of. Blood Adv. 2019;3:2164\u201378.","journal-title":"Blood Adv"},{"key":"2003_CR48","doi-asserted-by":"publisher","first-page":"6359","DOI":"10.1038\/onc.2016.189","volume":"35","author":"Y Meng","year":"2016","unstructured":"Meng Y, Wang L, Chen D, Chang Y, Zhang M, Xu JJ, et al. LAPTM4B: an oncogene in various solid tumors and its functions. Oncogene. 2016;35:6359\u201365.","journal-title":"Oncogene."},{"key":"2003_CR49","doi-asserted-by":"publisher","first-page":"87364","DOI":"10.18632\/oncotarget.20957","volume":"8","author":"S Lang","year":"2017","unstructured":"Lang S, Busch H, Boerries M, Brummer T, Timme S, Lassmann S, et al. Specific role of RhoC in tumor invasion and metastasis. Oncotarget. 2017;8:87364\u201378.","journal-title":"Oncotarget."}],"container-title":["Leukemia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41375-023-02003-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-023-02003-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-023-02003-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T13:04:27Z","timestamp":1695906267000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41375-023-02003-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,26]]},"references-count":49,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["2003"],"URL":"https:\/\/doi.org\/10.1038\/s41375-023-02003-x","relation":{},"ISSN":["0887-6924","1476-5551"],"issn-type":[{"value":"0887-6924","type":"print"},{"value":"1476-5551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,26]]},"assertion":[{"value":"30 March 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2023","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 August 2023","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 August 2023","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}