{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T07:26:47Z","timestamp":1792567607246,"version":"4.5.0"},"reference-count":114,"publisher":"American Society of Hematology","issue":"6","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,2,8]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>DNA-damaging agents have represented the first effective treatment for the blood cancer multiple myeloma, and after 65 years since their introduction to the clinic, they remain one of the mainstay therapies for this disease. Myeloma is a cancer of plasma cells. Despite exceedingly slow proliferation, myeloma cells present extended genomic rearrangements and intense genomic instability, starting at the premalignant stage of the disease. Where does such DNA damage stem from? A reliable model argues that the powerful oncogenes activated in myeloma as well the phenotypic peculiarities of cancer plasma cells, including the dependency on the proteasome for survival and the constant presence of oxidative stress, all converge on modulating DNA damage and repair. Beleaguered by these contraposing forces, myeloma cells survive in a precarious balance, in which the robust engagement of DNA repair mechanisms to guarantee cell survival is continuously challenged by rampant genomic instability, essential for cancer cells to withstand hostile selective pressures. Shattering this delicate equilibrium has been the goal of the extensive use of DNA-damaging agents since their introduction in the clinic, now enriched by novel approaches that leverage upon synthetic lethality paradigms. Exploiting the impairment of homologous recombination caused by myeloma genetic lesions or treatments, it is now possible to design therapeutic combinations that could target myeloma cells more effectively. Furthermore, DNA-damaging agents, as demonstrated in solid tumors, may sensitize cells to immune therapies. In all, targeting DNA damage and repair remains as central as ever in myeloma, even for the foreseeable future.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2023021384","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T19:31:11Z","timestamp":1700681471000},"page":"488-495","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":12,"title":["Myeloma and DNA damage"],"prefix":"10.1182","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2973-5038","authenticated-orcid":false,"given":"Giovanni","family":"Tonon","sequence":"first","affiliation":[{"name":"1Universit\u00e0 Vita-Salute San Raffaele, Milan, Italy"},{"name":"2Division of Experimental Oncology and Center for Omics Sciences, Functional Genomics of Cancer Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"11","key":"2024020816242185900_bib1","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.1038\/s41375-020-0921-y","article-title":"Genome instability in multiple myeloma","volume":"34","author":"Neuse","year":"2020","journal-title":"Leukemia"},{"issue":"7463","key":"2024020816242185900_bib2","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of mutational processes in human cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature"},{"issue":"1","key":"2024020816242185900_bib3","doi-asserted-by":"crossref","first-page":"17046","DOI":"10.1038\/nrdp.2017.46","article-title":"Multiple myeloma","volume":"3","author":"Kumar","year":"2017","journal-title":"Nat Rev Dis Primers"},{"issue":"6","key":"2024020816242185900_bib4","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.1182\/blood-2007-10-078022","article-title":"Multiple myeloma","volume":"111","author":"Kyle","year":"2008","journal-title":"Blood"},{"issue":"11","key":"2024020816242185900_bib5","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1056\/NEJMra1011442","article-title":"Multiple myeloma","volume":"364","author":"Palumbo","year":"2011","journal-title":"N\u00a0Engl J Med"},{"issue":"7339","key":"2024020816242185900_bib6","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nature09837","article-title":"Initial genome sequencing and analysis of multiple myeloma","volume":"471","author":"Chapman","year":"2011","journal-title":"Nature"},{"issue":"1","key":"2024020816242185900_bib7","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ccr.2013.12.015","article-title":"Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy","volume":"25","author":"Lohr","year":"2014","journal-title":"Cancer Cell"},{"issue":"1","key":"2024020816242185900_bib8","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.1038\/s41467-018-05058-y","article-title":"Genomic patterns of progression in smoldering multiple myeloma","volume":"9","author":"Bolli","year":"2018","journal-title":"Nat Commun"},{"issue":"33","key":"2024020816242185900_bib9","doi-asserted-by":"crossref","first-page":"3911","DOI":"10.1200\/JCO.2014.59.1503","article-title":"Mutational spectrum, copy number changes, and outcome: results of a sequencing study of patients with newly diagnosed myeloma","volume":"33","author":"Walker","year":"2015","journal-title":"J\u00a0Clin Oncol"},{"issue":"2","key":"2024020816242185900_bib10","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nrclinonc.2016.122","article-title":"Genomic complexity of multiple myeloma and its clinical implications","volume":"14","author":"Manier","year":"2017","journal-title":"Nat Rev Clin Oncol"},{"issue":"4","key":"2024020816242185900_bib11","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.ccr.2006.03.019","article-title":"High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients","volume":"9","author":"Carrasco","year":"2006","journal-title":"Cancer Cell"},{"issue":"8","key":"2024020816242185900_bib12","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1038\/leu.2011.94","article-title":"Evidence for ongoing DNA damage in multiple myeloma cells as revealed by constitutive phosphorylation of H2AX","volume":"25","author":"Walters","year":"2011","journal-title":"Leukemia"},{"issue":"6","key":"2024020816242185900_bib13","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/nm.3562","article-title":"Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers","volume":"20","author":"Cottini","year":"2014","journal-title":"Nat Med"},{"issue":"40","key":"2024020816242185900_bib14","doi-asserted-by":"crossref","first-page":"5611","DOI":"10.1038\/sj.onc.1204641","article-title":"Chromosome translocations in multiple myeloma","volume":"20","author":"Bergsagel","year":"2001","journal-title":"Oncogene"},{"issue":"1","key":"2024020816242185900_bib15","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1073\/pnas.97.1.228","article-title":"Diverse karyotypic abnormalities of the c-myc locus associated with c-myc dysregulation and tumor progression in multiple myeloma","volume":"97","author":"Shou","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024020816242185900_bib16","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.semcdb.2021.04.014","article-title":"Chromothripsis as a pathogenic driver of multiple myeloma","volume":"123","author":"Maura","year":"2022","journal-title":"Semin Cell Dev Biol"},{"issue":"7484","key":"2024020816242185900_bib17","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nature12912","article-title":"Discovery and saturation analysis of cancer genes across 21 tumour types","volume":"505","author":"Lawrence","year":"2014","journal-title":"Nature"},{"issue":"6","key":"2024020816242185900_bib18","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1002\/1097-0142(197212)30:6<1588::AID-CNCR2820300626>3.0.CO;2-Y","article-title":"Plasma cell myeloma. An interpretive review","volume":"30","author":"Bergsagel","year":"1972","journal-title":"Cancer"},{"key":"2024020816242185900_bib19","first-page":"845","article-title":"Cell proliferation in multiple myeloma studied with tritiated thymidine in\u00a0vivo","volume":"11","author":"Killmann","year":"1962","journal-title":"Lab Invest"},{"issue":"6","key":"2024020816242185900_bib20","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1172\/JCI106327","article-title":"Immunoglobulin synthesis and total body tumor cell number in IgG multiple myeloma","volume":"49","author":"Salmon","year":"1970","journal-title":"J\u00a0Clin Invest"},{"issue":"6","key":"2024020816242185900_bib21","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.molcel.2017.05.015","article-title":"ATM, ATR, and DNA-PK: the trinity at the heart of the DNA damage response","volume":"66","author":"Blackford","year":"2017","journal-title":"Mol Cell"},{"issue":"3","key":"2024020816242185900_bib22","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/nrc2342","article-title":"DNA repair pathways as targets for cancer therapy","volume":"8","author":"Helleday","year":"2008","journal-title":"Nat Rev Cancer"},{"issue":"7267","key":"2024020816242185900_bib23","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/nature08467","article-title":"The DNA-damage response in human biology and disease","volume":"461","author":"Jackson","year":"2009","journal-title":"Nature"},{"issue":"2","key":"2024020816242185900_bib24","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41568-022-00535-5","article-title":"Targeting DNA damage response pathways in cancer","volume":"23","author":"Groelly","year":"2023","journal-title":"Nat Rev Cancer"},{"issue":"11","key":"2024020816242185900_bib25","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1101\/gad.260703.115","article-title":"A\u00a0localized nucleolar DNA damage response facilitates recruitment of the homology-directed repair machinery independent of cell cycle stage","volume":"29","author":"Van Sluis","year":"2015","journal-title":"Genes Dev"},{"issue":"7890","key":"2024020816242185900_bib26","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/s41586-021-04200-z","article-title":"Activation of homologous recombination in G1 preserves centromeric integrity","volume":"600","author":"Yilmaz","year":"2021","journal-title":"Nature"},{"issue":"13","key":"2024020816242185900_bib27","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1111\/febs.13317","article-title":"Connecting by breaking and repairing: mechanisms of DNA strand exchange in meiotic recombination","volume":"282","author":"Sansam","year":"2015","journal-title":"FEBS J"},{"issue":"17","key":"2024020816242185900_bib28","doi-asserted-by":"crossref","first-page":"2760","DOI":"10.4161\/cc.25951","article-title":"DNA repair pathways in human multiple myeloma: role in oncogenesis and potential targets for treatment","volume":"12","author":"Gourzones-Dmitriev","year":"2013","journal-title":"Cell Cycle"},{"issue":"16","key":"2024020816242185900_bib29","doi-asserted-by":"crossref","first-page":"4155","DOI":"10.3390\/cancers15164155","article-title":"Understanding DNA damage response and DNA repair in multiple myeloma","volume":"15","author":"Petrilla","year":"2023","journal-title":"Cancers (Basel)"},{"issue":"5","key":"2024020816242185900_bib30","doi-asserted-by":"crossref","first-page":"a026070","DOI":"10.1101\/cshperspect.a026070","article-title":"p53 in the DNA-damage-repair process","volume":"6","author":"Williams","year":"2016","journal-title":"Cold Spring Harb Perspect Med"},{"issue":"10","key":"2024020816242185900_bib31","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1182\/blood-2007-05-089193","article-title":"Dysfunctional homologous recombination mediates genomic instability and progression in myeloma","volume":"113","author":"Shammas","year":"2009","journal-title":"Blood"},{"issue":"1","key":"2024020816242185900_bib32","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/s41375-019-0542-5","article-title":"Long non-coding RNA NEAT1 targeting impairs the DNA repair machinery and triggers anti-tumor activity in multiple myeloma","volume":"34","author":"Taiana","year":"2020","journal-title":"Leukemia"},{"issue":"9","key":"2024020816242185900_bib33","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.3390\/cancers13092127","article-title":"Genomic instability in multiple myeloma: a \u201cnon-coding RNA\u201d perspective","volume":"13","author":"Taiana","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"2","key":"2024020816242185900_bib34","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/s41375-018-0238-2","article-title":"miR-22 suppresses DNA ligase III addiction in multiple myeloma","volume":"33","author":"Caracciolo","year":"2019","journal-title":"Leukemia"},{"issue":"10","key":"2024020816242185900_bib35","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1038\/leu.2017.54","article-title":"RECQ1 helicase is involved in replication stress survival and drug resistance in multiple myeloma","volume":"31","author":"Viziteu","year":"2017","journal-title":"Leukemia"},{"issue":"9","key":"2024020816242185900_bib36","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1182\/blood-2015-06-649970","article-title":"Evidence for a role of the histone deacetylase SIRT6 in DNA damage response of multiple myeloma cells","volume":"127","author":"Cea","year":"2016","journal-title":"Blood"},{"issue":"1","key":"2024020816242185900_bib37","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1182\/blood-2005-01-0034","article-title":"Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma","volume":"106","author":"Bergsagel","year":"2005","journal-title":"Blood"},{"issue":"18","key":"2024020816242185900_bib38","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1182\/blood.2020010572","article-title":"Specific targeting of the KRAS mutational landscape in myeloma as a tool to unveil the elicited antitumor activity","volume":"138","author":"Sacco","year":"2021","journal-title":"Blood"},{"issue":"6","key":"2024020816242185900_bib39","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1038\/leu.2011.53","article-title":"Clinical and biological implications of MYC activation: a common difference between MGUS and newly diagnosed multiple myeloma","volume":"25","author":"Chng","year":"2011","journal-title":"Leukemia"},{"issue":"12","key":"2024020816242185900_bib40","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1182\/blood-2011-08-371567","article-title":"Addiction to c-MYC in multiple myeloma","volume":"120","author":"Holien","year":"2012","journal-title":"Blood"},{"issue":"12","key":"2024020816242185900_bib41","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1182\/blood-2012-08-445262","article-title":"MYC addiction: a potential therapeutic target in MM","volume":"120","author":"Kuehl","year":"2012","journal-title":"Blood"},{"issue":"1","key":"2024020816242185900_bib42","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1038\/s41375-019-0543-4","article-title":"MYC dysregulation in the progression of multiple myeloma","volume":"34","author":"Misund","year":"2020","journal-title":"Leukemia"},{"issue":"3","key":"2024020816242185900_bib43","doi-asserted-by":"crossref","first-page":"e191","DOI":"10.1038\/bcj.2014.13","article-title":"Translocations at 8q24 juxtapose MYC with genes that harbor superenhancers resulting in overexpression and poor prognosis in myeloma patients","volume":"4","author":"Walker","year":"2014","journal-title":"Blood Cancer J"},{"issue":"8","key":"2024020816242185900_bib44","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1038\/leu.2014.70","article-title":"Promiscuous MYC locus rearrangements hijack enhancers but mostly super-enhancers to dysregulate MYC expression in multiple myeloma","volume":"28","author":"Affer","year":"2014","journal-title":"Leukemia"},{"issue":"6","key":"2024020816242185900_bib45","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/nrd4553","article-title":"Exploiting replicative stress to treat cancer","volume":"14","author":"Dobbelstein","year":"2015","journal-title":"Nat Rev Drug Discov"},{"issue":"1","key":"2024020816242185900_bib46","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41573-022-00558-5","article-title":"Targeting replication stress in cancer therapy","volume":"22","author":"da Costa","year":"2023","journal-title":"Nat Rev Drug Discov"},{"issue":"5","key":"2024020816242185900_bib47","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1158\/2159-8290.CD-17-1461","article-title":"Mechanisms of oncogene-induced replication stress: jigsaw falling into place","volume":"8","author":"Kotsantis","year":"2018","journal-title":"Cancer Discov"},{"issue":"10","key":"2024020816242185900_bib48","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.3324\/haematol.2018.215210","article-title":"ATR addiction in multiple myeloma: synthetic lethal approaches exploiting established therapies","volume":"105","author":"Botrugno","year":"2019","journal-title":"Haematologica"},{"issue":"1","key":"2024020816242185900_bib49","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3390\/cancers14010025","article-title":"Genomic instability and replicative stress in multiple myeloma: the final curtain?","volume":"14","author":"Botrugno","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"9","key":"2024020816242185900_bib50","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1158\/2159-8290.CD-14-0943","article-title":"Synthetic lethal approaches exploiting DNA damage in aggressive myeloma","volume":"5","author":"Cottini","year":"2015","journal-title":"Cancer Discov"},{"issue":"7694","key":"2024020816242185900_bib51","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nature25507","article-title":"Intragenic origins due to short G1 phases underlie oncogene-induced DNA replication stress","volume":"555","author":"Macheret","year":"2018","journal-title":"Nature"},{"issue":"5","key":"2024020816242185900_bib52","first-page":"758","article-title":"Inactivation of tumor suppressor genes, p53 and Rb1, in plasma cell dyscrasias","volume":"8","author":"Corradini","year":"1994","journal-title":"Leukemia"},{"issue":"5868","key":"2024020816242185900_bib53","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1126\/science.1140735","article-title":"An oncogene-induced DNA damage model for cancer development","volume":"319","author":"Halazonetis","year":"2008","journal-title":"Science"},{"key":"2024020816242185900_bib54","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/bs.apcsb.2018.10.006","article-title":"Replication stress: driver and therapeutic target in genomically instable cancers","volume":"115","author":"Schoonen","year":"2019","journal-title":"Adv Protein Chem Struct Biol"},{"issue":"45","key":"2024020816242185900_bib55","doi-asserted-by":"crossref","first-page":"eadd3686","DOI":"10.1126\/sciadv.add3686","article-title":"DNA replication initiation shapes the mutational landscape and expression of the human genome","volume":"8","author":"Murat","year":"2022","journal-title":"Sci Adv"},{"issue":"5","key":"2024020816242185900_bib56","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/S1097-2765(02)00520-8","article-title":"c-Myc can induce DNA damage, increase reactive oxygen species, and mitigate p53 function: a mechanism for oncogene-induced genetic instability","volume":"9","author":"Vafa","year":"2002","journal-title":"Mol Cell"},{"issue":"17","key":"2024020816242185900_bib57","doi-asserted-by":"crossref","first-page":"9974","DOI":"10.1073\/pnas.1732638100","article-title":"Defective double-strand DNA break repair and chromosomal translocations by MYC overexpression","volume":"100","author":"Karlsson","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"2024020816242185900_bib58","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1080\/15384101.2019.1706903","article-title":"The double dealing of cyclin D1","volume":"19","author":"Tchakarska","year":"2020","journal-title":"Cell Cycle"},{"key":"2024020816242185900_bib59","doi-asserted-by":"crossref","first-page":"751367","DOI":"10.3389\/fcell.2022.751367","article-title":"The influence of oncogenic RAS on chemotherapy and radiotherapy resistance through DNA repair pathways","volume":"10","author":"C\u00e1ceres-Guti\u00e9rrez","year":"2022","journal-title":"Front Cell Dev Biol"},{"issue":"2","key":"2024020816242185900_bib60","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ccr.2007.07.003","article-title":"Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myeloma","volume":"12","author":"Keats","year":"2007","journal-title":"Cancer Cell"},{"issue":"2","key":"2024020816242185900_bib61","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ccr.2007.07.004","article-title":"Frequent engagement of the classical and alternative NF-kappaB pathways by diverse genetic abnormalities in multiple myeloma","volume":"12","author":"Annunziata","year":"2007","journal-title":"Cancer Cell"},{"issue":"19","key":"2024020816242185900_bib62","doi-asserted-by":"crossref","first-page":"11075","DOI":"10.3390\/ijms231911075","article-title":"NSD2 as a promising target in hematological disorders","volume":"23","author":"Azagra","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"9","key":"2024020816242185900_bib63","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1182\/blood.V92.9.3025","article-title":"The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH\/MMSET hybrid transcripts","volume":"92","author":"Chesi","year":"1998","journal-title":"Blood"},{"issue":"6","key":"2024020816242185900_bib64","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.1182\/blood-2002-09-2801","article-title":"A\u00a0subset of multiple myeloma harboring the t(4;14)(p16;q32) translocation lacks FGFR3 expression but maintains anIGH\/MMSET fusion transcript","volume":"101","author":"Santra","year":"2003","journal-title":"Blood"},{"issue":"7332","key":"2024020816242185900_bib65","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/nature09658","article-title":"MMSET regulates histone H4K20 methylation and 53BP1 accumulation at DNA damage sites","volume":"470","author":"Pei","year":"2011","journal-title":"Nature"},{"issue":"32","key":"2024020816242185900_bib66","doi-asserted-by":"crossref","first-page":"13130","DOI":"10.1073\/pnas.1110081108","article-title":"Wolf-Hirschhorn syndrome candidate 1 is involved in the cellular response to DNA damage","volume":"108","author":"Hajdu","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"45","key":"2024020816242185900_bib67","doi-asserted-by":"crossref","first-page":"5905","DOI":"10.1038\/onc.2016.116","article-title":"MMSET\/WHSC1 enhances DNA damage repair leading to an increase in resistance to chemotherapeutic agents","volume":"35","author":"Shah","year":"2016","journal-title":"Oncogene"},{"issue":"3","key":"2024020816242185900_bib68","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/leu.2012.269","article-title":"MMSET stimulates myeloma cell growth through microRNA-mediated modulation of c-MYC","volume":"27","author":"Min","year":"2013","journal-title":"Leukemia"},{"issue":"48","key":"2024020816242185900_bib69","doi-asserted-by":"crossref","first-page":"6212","DOI":"10.1038\/s41388-018-0393-y","article-title":"Methylation of Aurora kinase A by MMSET reduces p53 stability and regulates cell proliferation and apoptosis","volume":"37","author":"Park","year":"2018","journal-title":"Oncogene"},{"issue":"4","key":"2024020816242185900_bib70","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrm.2015.15","article-title":"The regulation and functions of the nuclear RNA exosome complex","volume":"17","author":"Kilchert","year":"2016","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"2","key":"2024020816242185900_bib71","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1093\/nar\/gkt930","article-title":"Multiple myeloma-associated hDIS3 mutations cause perturbations in cellular RNA metabolism and suggest hDIS3 PIN domain as a potential drug target","volume":"42","author":"Tomecki","year":"2014","journal-title":"Nucleic Acids Res"},{"issue":"10","key":"2024020816242185900_bib72","doi-asserted-by":"crossref","first-page":"5182","DOI":"10.1093\/nar\/gkv387","article-title":"The ribonuclease DIS3 promotes let-7 miRNA maturation by degrading the pluripotency factor LIN28B mRNA","volume":"43","author":"Segalla","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"72","key":"2024020816242185900_bib73","doi-asserted-by":"crossref","first-page":"eabn2738","DOI":"10.1126\/sciimmunol.abn2738","article-title":"RNA exosome drives early B cell development via noncoding RNA processing mechanisms","volume":"7","author":"Laffleur","year":"2022","journal-title":"Sci Immunol"},{"issue":"2","key":"2024020816242185900_bib74","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/s41588-020-00772-0","article-title":"Noncoding RNA processing by DIS3 regulates chromosomal architecture and somatic hypermutation in B cells","volume":"53","author":"Laffleur","year":"2021","journal-title":"Nat Genet"},{"issue":"1","key":"2024020816242185900_bib75","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1080\/19491034.2019.1578600","article-title":"Exonuclease domain mutants of yeast DIS3 display genome instability","volume":"10","author":"Milbury","year":"2019","journal-title":"Nucleus"},{"issue":"1","key":"2024020816242185900_bib76","first-page":"231","article-title":"DIS3 depletion in multiple myeloma causes extensive perturbation in cell cycle progression and centrosome amplification","volume":"109","author":"Favasuli","year":"2024","journal-title":"Haematologica"},{"issue":"22","key":"2024020816242185900_bib77","doi-asserted-by":"crossref","first-page":"e108040","DOI":"10.15252\/embj.2021108040","article-title":"Loss of ribonuclease DIS3 hampers genome integrity in myeloma by disrupting DNA:RNA hybrid metabolism","volume":"41","author":"Gritti","year":"2022","journal-title":"EMBO J"},{"issue":"3","key":"2024020816242185900_bib78","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.cell.2019.08.055","article-title":"R\u00a0loops: from physiological to pathological roles","volume":"179","author":"Garc\u0131a-Muse","year":"2019","journal-title":"Cell"},{"issue":"22","key":"2024020816242185900_bib79","doi-asserted-by":"crossref","first-page":"e109711","DOI":"10.15252\/embj.2021109711","article-title":"AATF \/Che-1 localizes to paraspeckles and suppresses R-loops accumulation and interferon activation in multiple myeloma","volume":"41","author":"Bruno","year":"2022","journal-title":"EMBO J"},{"issue":"5","key":"2024020816242185900_bib80","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/ng.349","article-title":"Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer","volume":"41","author":"van Haaften","year":"2009","journal-title":"Nat Genet"},{"issue":"4","key":"2024020816242185900_bib81","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/s41375-023-01833-z","article-title":"KDM6 demethylases integrate DNA repair gene regulation and loss of KDM6A sensitizes human acute myeloid leukemia to PARP and BCL2 inhibition","volume":"37","author":"Boila","year":"2023","journal-title":"Leukemia"},{"issue":"11","key":"2024020816242185900_bib82","doi-asserted-by":"crossref","first-page":"e78652","DOI":"10.1371\/journal.pone.0078652","article-title":"Drosophila UTX coordinates with p53 to regulate ku80 expression in response to DNA damage","volume":"8","author":"Zhang","year":"2013","journal-title":"PLoS One"},{"issue":"6","key":"2024020816242185900_bib83","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.ccell.2016.05.005","article-title":"YAP\/TAZ at the roots of cancer","volume":"29","author":"Zanconato","year":"2016","journal-title":"Cancer Cell"},{"issue":"6","key":"2024020816242185900_bib84","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1182\/blood-2018-03-840132","article-title":"Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma","volume":"132","author":"Walker","year":"2018","journal-title":"Blood"},{"issue":"6","key":"2024020816242185900_bib85","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.cell.2007.09.007","article-title":"Non-oncogene addiction and the stress phenotype of cancer cells","volume":"130","author":"Solimini","year":"2007","journal-title":"Cell"},{"issue":"5","key":"2024020816242185900_bib86","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.cell.2009.02.024","article-title":"Principles of cancer therapy: oncogene and non-oncogene addiction","volume":"136","author":"Luo","year":"2009","journal-title":"Cell"},{"issue":"12","key":"2024020816242185900_bib87","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1182\/blood-2014-05-578732","article-title":"The Tao of myeloma","volume":"124","author":"Boise","year":"2014","journal-title":"Blood"},{"issue":"13","key":"2024020816242185900_bib88","doi-asserted-by":"crossref","first-page":"3040","DOI":"10.1182\/blood-2008-08-172734","article-title":"The proteasome load versus capacity balance determines apoptotic sensitivity of multiple myeloma cells to proteasome inhibition","volume":"113","author":"Bianchi","year":"2009","journal-title":"Blood"},{"issue":"12","key":"2024020816242185900_bib89","doi-asserted-by":"crossref","first-page":"4907","DOI":"10.1182\/blood-2005-08-3531","article-title":"Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells","volume":"107","author":"Obeng","year":"2006","journal-title":"Blood"},{"issue":"18","key":"2024020816242185900_bib90","doi-asserted-by":"crossref","first-page":"8536","DOI":"10.1158\/0008-5472.CAN-07-1166","article-title":"Inhibitors of the proteasome suppress homologous DNA recombination in mammalian cells","volume":"67","author":"Murakawa","year":"2007","journal-title":"Cancer Res"},{"issue":"15","key":"2024020816242185900_bib91","doi-asserted-by":"crossref","first-page":"7395","DOI":"10.1158\/0008-5472.CAN-07-1015","article-title":"Proteasome function is required for DNA damage response and Fanconi anemia pathway activation","volume":"67","author":"Jacquemont","year":"2007","journal-title":"Cancer Res"},{"issue":"5","key":"2024020816242185900_bib92","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/s41568-021-00435-0","article-title":"The role of ROS in tumour development and progression","volume":"22","author":"Cheung","year":"2022","journal-title":"Nat Rev Cancer"},{"issue":"8","key":"2024020816242185900_bib93","doi-asserted-by":"crossref","first-page":"3883","DOI":"10.1007\/s00018-021-03756-3","article-title":"Crosstalk between endoplasmic reticulum stress and oxidative stress: a dynamic duo in multiple myeloma","volume":"78","author":"Xiong","year":"2021","journal-title":"Cell Mol Life Sci"},{"issue":"7047","key":"2024020816242185900_bib94","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nature03688","article-title":"Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability","volume":"436","author":"Radisky","year":"2005","journal-title":"Nature"},{"issue":"50","key":"2024020816242185900_bib95","doi-asserted-by":"crossref","first-page":"20401","DOI":"10.1073\/pnas.1211532109","article-title":"A\u00a0switch between DNA polymerases \u03b4 and \u03bb promotes error-free bypass of 8-oxo-G lesions","volume":"109","author":"Markkanen","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"2024020816242185900_bib96","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1111\/j.1365-2141.2007.06772.x","article-title":"The histone deacetylase inhibitor, PXD101, potentiates bortezomib-induced anti-multiple myeloma effect by induction of oxidative stress and DNA damage: combination of bortezomib and PXD101 against MM","volume":"139","author":"Feng","year":"2007","journal-title":"Br J Haematol"},{"issue":"11","key":"2024020816242185900_bib97","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1158\/0008-5472.CAN-19-2714","article-title":"FGF trapping inhibits multiple myeloma growth through c-Myc degradation\u2013induced mitochondrial oxidative stress","volume":"80","author":"Ronca","year":"2020","journal-title":"Cancer Res"},{"issue":"3","key":"2024020816242185900_bib98","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1111\/j.1749-6632.1958.tb42675.x","article-title":"Clinical experiences with sarcolysin in neoplastic diseases","volume":"68","author":"Blokhin","year":"1958","journal-title":"Ann N Y Acad Sci"},{"key":"2024020816242185900_bib99","first-page":"87","article-title":"Evaluation of new chemotherapeutic agents in the treatment of multiple myeloma. IV. L-Phenylalanine mustard (NSC-8806)","volume":"21","author":"Bergsagel","year":"1962","journal-title":"Cancer Chemother Rep"},{"issue":"9","key":"2024020816242185900_bib100","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1001\/jama.1969.03160090040009","article-title":"Treatment for multiple myeloma. Combination chemotherapy with different melphalan dose regimens","volume":"208","author":"Alexanian","year":"1969","journal-title":"JAMA"},{"issue":"7","key":"2024020816242185900_bib101","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1586\/14737140.7.7.945","article-title":"Melphalan and its role in the management of patients with multiple myeloma","volume":"7","author":"Falco","year":"2007","journal-title":"Expert Rev Anticancer Ther"},{"issue":"12","key":"2024020816242185900_bib102","doi-asserted-by":"crossref","first-page":"3832","DOI":"10.1200\/JCO.1998.16.12.3832","article-title":"Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. Myeloma Trialists\u2019 Collaborative Group","volume":"16","year":"1998","journal-title":"J\u00a0Clin Oncol"},{"issue":"1","key":"2024020816242185900_bib103","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/leu.2017.182","article-title":"Nucleotide excision repair is a potential therapeutic target in multiple myeloma","volume":"32","author":"Szalat","year":"2018","journal-title":"Leukemia"},{"issue":"10","key":"2024020816242185900_bib104","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41408-018-0129-9","article-title":"Role of apurinic\/apyrimidinic nucleases in the regulation of homologous recombination in myeloma: mechanisms and translational significance","volume":"8","author":"Kumar","year":"2018","journal-title":"Blood Cancer J"},{"issue":"24","key":"2024020816242185900_bib105","doi-asserted-by":"crossref","first-page":"9367","DOI":"10.1158\/0008-5472.CAN-09-2616","article-title":"Targeting the Fanconi anemia\/BRCA pathway circumvents drug resistance in multiple myeloma","volume":"69","author":"Yarde","year":"2009","journal-title":"Cancer Res"},{"issue":"22","key":"2024020816242185900_bib106","first-page":"7900","article-title":"Genotypic and phenotypic comparisons of de novo and acquired melphalan resistance in an isogenic multiple myeloma cell line model","volume":"63","author":"Hazlehurst","year":"2003","journal-title":"Cancer Res"},{"issue":"9","key":"2024020816242185900_bib107","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/nrc1691","article-title":"The concept of synthetic lethality in the context of anticancer therapy","volume":"5","author":"Kaelin","year":"2005","journal-title":"Nat Rev Cancer"},{"issue":"1","key":"2024020816242185900_bib108","doi-asserted-by":"crossref","first-page":"185","DOI":"10.3324\/haematol.2019.240713","article-title":"Exploiting MYC-induced PARPness to target genomic instability in multiple myeloma","volume":"106","author":"Caracciolo","year":"2021","journal-title":"Haematologica"},{"issue":"2","key":"2024020816242185900_bib109","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1158\/1541-7786.MCR-17-0382","article-title":"Novel YAP1 activator, identified by transcription-based functional screen, limits multiple myeloma growth","volume":"16","author":"Maruyama","year":"2018","journal-title":"Mol Cancer Res"},{"issue":"24","key":"2024020816242185900_bib110","doi-asserted-by":"crossref","first-page":"6368","DOI":"10.1182\/blood-2011-06-363911","article-title":"Bortezomib-induced \u201cBRCAness\u201d sensitizes multiple myeloma cells to PARP inhibitors","volume":"118","author":"Neri","year":"2011","journal-title":"Blood"},{"issue":"4","key":"2024020816242185900_bib111","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/s41568-022-00544-4","article-title":"Mechanisms driving the immunoregulatory function of cancer cells","volume":"23","author":"van Weverwijk","year":"2023","journal-title":"Nat Rev Cancer"},{"issue":"7970","key":"2024020816242185900_bib112","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/s41586-023-06069-6","article-title":"The complementarity of DDR, nucleic acids and anti-tumour immunity","volume":"619","author":"Kornepati","year":"2023","journal-title":"Nature"},{"issue":"19","key":"2024020816242185900_bib113","doi-asserted-by":"crossref","first-page":"4787","DOI":"10.3390\/cancers13194787","article-title":"Keeping myeloma in check: the past, present and future of immunotherapy in multiple myeloma","volume":"13","author":"Ackley","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"11","key":"2024020816242185900_bib114","doi-asserted-by":"crossref","first-page":"3019","DOI":"10.1158\/1078-0432.CCR-12-3752","article-title":"In\u00a0vitro and in\u00a0vivo antitumor activity of a novel alkylating agent, melphalan-flufenamide, against multiple myeloma cells","volume":"19","author":"Chauhan","year":"2013","journal-title":"Clin Cancer Res"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2023021384\/2211223\/blood_bld-2023-021384-c-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2023021384\/2211223\/blood_bld-2023-021384-c-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T16:25:25Z","timestamp":1707409525000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/143\/6\/488\/498852\/Myeloma-and-DNA-damage"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,8]]},"references-count":114,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,2,8]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2023021384","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,8]]}}}