{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:36:15Z","timestamp":1791412575299,"version":"4.3.3"},"reference-count":135,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T00:00:00Z","timestamp":1670544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["2017-CE15-0024-01, ANR-18-CE15-0010-01"],"award-info":[{"award-number":["2017-CE15-0024-01, ANR-18-CE15-0010-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006364","name":"Institut National Du Cancer","doi-asserted-by":"publisher","award":["PLBIO18-362PIT-MM , FATidique"],"award-info":[{"award-number":["PLBIO18-362PIT-MM , FATidique"]}],"id":[{"id":"10.13039\/501100006364","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Multiple myeloma (MM) is a hematologic cancer characterized by accumulation of malignant plasma cells in the bone marrow. To date, no definitive cure exists for MM and resistance to current treatments is one of the major challenges of this disease. The DNA helicase BLM, whose depletion or mutation causes the cancer-prone Bloom\u2019s syndrome (BS), is a central factor of DNA damage repair by homologous recombination (HR) and genomic stability maintenance. Using independent cohorts of MM patients, we identified that high expression of BLM is associated with a poor outcome with a significant enrichment in replication stress signature. We provide evidence that chemical inhibition of BLM by the small molecule ML216 in HMCLs (human myeloma cell lines) leads to cell cycle arrest and increases apoptosis, likely by accumulation of DNA damage. BLM inhibition synergizes with the alkylating agent melphalan to efficiently inhibit growth and promote cell death in HMCLs. Moreover, ML216 treatment re-sensitizes melphalan-resistant cell lines to this conventional therapeutic agent. Altogether, these data suggest that inhibition of BLM in combination with DNA damaging agents could be of therapeutic interest in the treatment of MM, especially in those patients with high BLM expression and\/or resistance to melphalan.<\/jats:p>","DOI":"10.3389\/fimmu.2022.983181","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T07:14:10Z","timestamp":1670570050000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["The BLM helicase is a new therapeutic target in multiple myeloma involved in replication stress survival and drug resistance"],"prefix":"10.3389","volume":"13","author":[{"given":"Sara","family":"Ovejero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Viziteu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Dutrieux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Devin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yea-Lih","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elina","family":"Alaterre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Jourdan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihane","family":"Basbous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilhem","family":"Requirand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Robert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugues","family":"de Boussac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Seckinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Hose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Herbaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelos","family":"Constantinou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Pasero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Moreaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12020407","article-title":"Multiple myeloma: Available therapies and causes of drug resistance","volume":"12","author":"Pinto","year":"2020","journal-title":"Cancers"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30295-5","article-title":"Redefining the treatment paradigm for multiple myeloma","volume":"20","author":"Gay","year":"2019","journal-title":"Lancet Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60493-1","article-title":"Multiple myeloma","volume":"385","author":"R\u00f6llig","year":"2015","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.313","article-title":"Continued improvement in survival in multiple myeloma: Changes in early mortality and outcomes in older patients","volume":"28","author":"Kumar","year":"2014","journal-title":"Leukemia"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(20)30323-9","article-title":"Bortezomib, thalidomide, and dexamethasone followed by double autologous haematopoietic stem-cell transplantation for newly diagnosed multiple myeloma (GIMEMA-MMY-3006): Long-term follow-up analysis of a randomised phase 3, open-label study","volume":"7","author":"Tacchetti","year":"2020","journal-title":"Lancet Haematol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402964","article-title":"Incomplete DJH rearrangements of the IgH gene are frequent in multiple myeloma patients: Immunobiological characteristics and clinical implications","volume":"17","author":"Gonz\u00e1lez","year":"2003","journal-title":"Leukemia"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1172\/JCI61188","article-title":"Molecular pathogenesis of multiple myeloma and its premalignant precursor","volume":"122","author":"Kuehl","year":"2012","journal-title":"J Clin Invest"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203782","article-title":"Adhesion to fibronectin via \u03b21 integrins regulates p27kip1 levels and contributes to cell adhesion mediated drug resistance (CAM-DR)","volume":"19","author":"Hazlehurst","year":"2000","journal-title":"Oncogene"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.3.1104.bloodjournal8731104","article-title":"Multiple myeloma cell adhesion-induced interleukin-6 expression in bone marrow stromal cells involves activation of NF-kappa b","volume":"87","author":"Chauhan","year":"1996","journal-title":"Blood"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-10-745059","article-title":"Bone marrow microenvironment\u2013derived signals induce mcl-1 dependence in multiple myeloma","volume":"129","author":"Gupta","year":"2017","journal-title":"Blood"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26080","article-title":"New regimens and directions in the management of newly diagnosed multiple myeloma","volume":"96","author":"Bal","year":"2021","journal-title":"Am J Hematol"},{"key":"B12","doi-asserted-by":"publisher","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"},{"key":"B13","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1186\/s13148-018-0554-4","article-title":"PRC2 targeting is a therapeutic strategy for EZ score defined high-risk multiple myeloma patients and overcome resistance to IMiDs","volume":"10","author":"Herviou","year":"2018","journal-title":"Clin Epigenet"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-018-0025-x","article-title":"DNMTi\/HDACi combined epigenetic targeted treatment induces reprogramming of myeloma cells in the direction of normal plasma cells","volume":"118","author":"Bruyer","year":"2018","journal-title":"Br J Cancer"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2017.09.007","article-title":"Epigenetics in multiple myeloma: From mechanisms to therapy","volume":"51","author":"Alzrigat","year":"2018","journal-title":"Semin Cancer Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergencyto.2005.02.015","article-title":"High incidence and intraclonal heterogeneity of chromosome 11 aberrations in patients with newly diagnosed multiple myeloma detected by multiprobe interphase FISH","volume":"161","author":"Cremer","year":"2005","journal-title":"Cancer Genet Cytogenet"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-405977","article-title":"Whole-genome sequencing of multiple myeloma from diagnosis to plasma cell leukemia reveals genomic initiating events, evolution, and clonal tides","volume":"120","author":"Egan","year":"2012","journal-title":"Blood"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-1066","article-title":"The progression from MGUS to smoldering myeloma and eventually to multiple myeloma involves a clonal expansion of genetically abnormal plasma cells","volume":"17","author":"Lopez-Corral","year":"2011","journal-title":"Clin Cancer Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.98","article-title":"Quantification of clonal circulating plasma cells in newly diagnosed multiple myeloma: Implications for redefining high-risk myeloma","volume":"28","author":"Gonsalves","year":"2014","journal-title":"Leukemia"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.49.30611","article-title":"The bloom\u2019s syndrome gene product is a 3\u2032-5\u2032 DNA helicase","volume":"272","author":"Karow","year":"1997","journal-title":"J Biol Chem"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2003811","article-title":"BLM\u2013DNA2\u2013RPA\u2013MRN and EXO1\u2013BLM\u2013RPA\u2013MRN constitute two DNA end resection machineries for human DNA break repair","volume":"25","author":"Nimonkar","year":"2011","journal-title":"Genes Dev"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060713-035428","article-title":"Human RecQ helicases in DNA repair, recombination, and replication","volume":"83","author":"Croteau","year":"2014","journal-title":"Annu Rev Biochem"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-021-01234-0","article-title":"RNA-Sequencing data-driven dissection of human plasma cell differentiation reveals new potential transcription regulators","volume":"35","author":"Kassambara","year":"2021","journal-title":"Leukemia"},{"key":"B24","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1146\/annurev-genet-102209-163602","article-title":"The RecQ DNA helicases in DNA repair","volume":"44","author":"Bernstein","year":"2010","journal-title":"Annu Rev Genet"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.640755","article-title":"Human RecQ helicases in DNA double-strand break repair","volume":"9","author":"Lu","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1172\/JCI147301","article-title":"RECON syndrome is a genome instability disorder caused by mutations in the DNA helicase RECQL1","volume":"132","author":"Abu-Libdeh","year":"2022","journal-title":"J Clin Invest"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202389","article-title":"Point mutations causing bloom\u2019s syndrome abolish ATPase and DNA helicase activities of the BLM protein","volume":"17","author":"Bahr","year":"1998","journal-title":"Oncogene"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.1954.02050100756008","article-title":"Congenital telangiectatic erythema resembling lupus erythematosus in dwarfs; probably a syndrome entity","volume":"88","author":"Bloom","year":"1954","journal-title":"AMA Am J Dis Child"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1126\/science.148.3669.506","article-title":"Chromosomal breakage in a rare and probably genetically determined syndrome of man","volume":"148","author":"German","year":"1965","journal-title":"Science"},{"key":"B30","first-page":"196","article-title":"Bloom\u2019s syndrome. i. genetical and clinical observations in the first twenty-seven patients","volume":"21","author":"German","year":"1969","journal-title":"Am J Hum Genet"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/BF00290993","article-title":"Bloom\u2019s syndrome. III. analysis of the chromosome aberration characteristic of this disorder","volume":"48","author":"German","year":"1974","journal-title":"Chromosoma"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.71.11.4508","article-title":"A manyfold increase in sister chromatid exchanges in bloom\u2019s syndrome lymphocytes","volume":"71","author":"Chaganti","year":"1974","journal-title":"Proc Natl Acad Sci USA"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/nature02253","article-title":"The bloom\u2019s syndrome helicase suppresses crossing over during homologous recombination","volume":"426","author":"Wu","year":"2003","journal-title":"Nature"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2018.1520567","article-title":"BLM\u2019s balancing act and the involvement of FANCJ in DNA repair","volume":"17","author":"Dhar","year":"2018","journal-title":"Cell Cycle"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1038\/s41467-018-03393-8","article-title":"MRN complex-dependent recruitment of ubiquitylated BLM helicase to DSBs negatively regulates DNA repair pathways","volume":"9","author":"Tripathi","year":"2018","journal-title":"Nat Commun"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1101\/gad.503108","article-title":"DNA Helicases Sgs1 and BLM promote DNA double-strand break resection","volume":"22","author":"Gravel","year":"2008","journal-title":"Genes Dev"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809380105","article-title":"Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair","volume":"105","author":"Nimonkar","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.100448097","article-title":"The bloom\u2019s syndrome gene product promotes branch migration of holliday junctions","volume":"97","author":"Karow","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"B39","doi-asserted-by":"publisher","first-page":"a016477","DOI":"10.1101\/cshperspect.a016477","article-title":"The dissolution of double holliday junctions","volume":"6","author":"Bizard","year":"2014","journal-title":"Cold Spring Harbor Perspect Biol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a016410","article-title":"An overview of the molecular mechanisms of recombinational DNA repair","volume":"7","author":"Kowalczykowski","year":"2015","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1609007","article-title":"Novel pro- and anti-recombination activities of the bloom\u2019s syndrome helicase","volume":"21","author":"Bugreev","year":"2007","journal-title":"Genes Dev"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl258","article-title":"Mobile d-loops are a preferred substrate for the bloom\u2019s syndrome helicase","volume":"34","author":"Bachrati","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1021\/bi0018640","article-title":"Binding and melting of d-loops by the bloom syndrome helicase","volume":"39","author":"van Brabant","year":"2000","journal-title":"Biochemistry"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201703144","article-title":"BLM helicase regulates DNA repair by counteracting RAD51 loading at DNA double-strand break sites","volume":"216","author":"Patel","year":"2017","journal-title":"J Cell Biol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1083\/jcb.200610051","article-title":"BLM helicase\u2013dependent and \u2013independent roles of 53BP1 during replication stress\u2013mediated homologous recombination","volume":"178","author":"Tripathi","year":"2007","journal-title":"J Cell Biol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M604268200","article-title":"The bloom\u2019s syndrome helicase can promote the regression of a model replication fork","volume":"281","author":"Ralf","year":"2006","journal-title":"J Biol Chem"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb1267","article-title":"Role for BLM in replication-fork restart and suppression of origin firing after replicative stress","volume":"14","author":"Davies","year":"2007","journal-title":"Nat Struct Mol Biol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200405128","article-title":"Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during s-phase arrest","volume":"166","author":"Sengupta","year":"2004","journal-title":"J Cell Biol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033905","article-title":"Bloom\u2019s syndrome and PICH helicases cooperate with topoisomerase II\u03b1 in centromere disjunction before anaphase","volume":"7","author":"Rouzeau","year":"2012","journal-title":"PloS One"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.226","article-title":"PICH and BLM limit histone association with anaphase centromeric DNA threads and promote their resolution: PICH and BLM limit histone association","volume":"30","author":"Ke","year":"2011","journal-title":"EMBO J"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601777","article-title":"BLM is required for faithful chromosome segregation and its localization defines a class of ultrafine anaphase bridges","volume":"26","author":"Chan","year":"2007","journal-title":"EMBO J"},{"key":"B52","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1083\/jcb.201410061","article-title":"BLM helicase facilitates telomere replication during leading strand synthesis of telomeres","volume":"210","author":"Drosopoulos","year":"2015","journal-title":"J Cell Biol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3390\/genes10110870","article-title":"Helicases FANCJ, RTEL1 and BLM act on guanine quadruplex DNA in vivo","volume":"10","author":"Lansdorp","year":"2019","journal-title":"Genes"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13738","article-title":"Resolution of ROS-induced G-quadruplexes and r-loops at transcriptionally active sites is dependent on BLM helicase","volume":"594","author":"Tan","year":"2020","journal-title":"FEBS Lett"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/35077232","article-title":"Genome maintenance mechanisms for preventing cancer","volume":"411","author":"Hoeijmakers","year":"2001","journal-title":"Nature"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3088","article-title":"DNA Interstrand crosslink repair and cancer","volume":"11","author":"Deans","year":"2011","journal-title":"Nat Rev Cancer"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2010.551155","article-title":"Abnormalities of DNA repair mechanisms in common hematological malignancies","volume":"52","author":"Economopoulou","year":"2011","journal-title":"Leuk Lymph"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.1740","article-title":"A DNA repair pathway score predicts survival in human multiple myeloma: the potential for therapeutic strategy","volume":"5","author":"Kassambara","year":"2014","journal-title":"Oncotarget"},{"key":"B59","doi-asserted-by":"publisher","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 Discovery"},{"key":"B60","doi-asserted-by":"publisher","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"},{"key":"B61","doi-asserted-by":"publisher","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"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-016-0057-4","article-title":"RECQ helicases are deregulated in hematological malignancies in association with a prognostic value","volume":"4","author":"Viziteu","year":"2016","journal-title":"biomark Res"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2013.08.025","article-title":"Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of bloom helicase","volume":"23","author":"Rosenthal","year":"2013","journal-title":"Bioorg Med Chem Lett"},{"key":"B64","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.chembiol.2012.10.016","article-title":"A small molecule inhibitor of the BLM helicase modulates chromosome stability in human cells","volume":"20","author":"Nguyen","year":"2013","journal-title":"Chem Biol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2010.033456","article-title":"A high-risk signature for patients with multiple myeloma established from the molecular classification of human myeloma cell lines","volume":"96","author":"Moreaux","year":"2011","journal-title":"Haematologica"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.7150\/thno.28374","article-title":"Comprehensive characterization of the mutational landscape in multiple myeloma cell lines reveals potential drivers and pathways associated with tumor progression and drug resistance","volume":"9","author":"Vikova","year":"2019","journal-title":"Theranostics"},{"key":"B67","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3324\/haematol.2010.030296","article-title":"Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma","volume":"96","author":"Hose","year":"2011","journal-title":"Haematologica"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004077","article-title":"GenomicScape: An easy-to-Use web tool for gene expression data analysis. application to investigate the molecular events in the differentiation of b cells into plasma cells","volume":"11","author":"Kassambara","year":"2015","journal-title":"PloS Comput Biol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.046821","article-title":"Genes with a spike expression are clustered in chromosome (sub)bands and spike (sub)bands have a powerful prognostic value in patients with multiple myeloma","volume":"97","author":"Kassambara","year":"2012","journal-title":"Haematologica"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.208306","article-title":"Kinome expression profiling to target new therapeutic avenues in multiple myeloma","volume":"105","author":"de Boussac","year":"2020","journal-title":"Haematologica"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-06-1984","article-title":"BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone","volume":"103","author":"Moreaux","year":"2004","journal-title":"Blood"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-11-013458","article-title":"The molecular classification of multiple myeloma","volume":"108","author":"Zhan","year":"2006","journal-title":"Blood"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.099358","article-title":"European Myeloma network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma","volume":"99","author":"Engelhardt","year":"2014","journal-title":"Haematologica"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-07-038430","article-title":"A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1","volume":"109","author":"Shaughnessy","year":"2007","journal-title":"Blood"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.13.8545","article-title":"Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: A study of the intergroupe francophone du my\u00e9lome","volume":"26","author":"Decaux","year":"2008","journal-title":"JCO"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt124","article-title":"Modeling risk stratification in human cancer","volume":"29","author":"R\u00e8me","year":"2013","journal-title":"Bioinformatics"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.21730","article-title":"BrdU incorporation in multiparameter flow cytometry: A new cell cycle assessment approach in multiple myeloma","volume":"96","author":"Requirand","year":"2019","journal-title":"Cytometry"},{"key":"B78","volume-title":"Integrative approach to find predictive markers of response to daratumumab in multiple myeloma","author":"Pochard","year":"2021"},{"key":"B79","doi-asserted-by":"publisher","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"},{"key":"B80","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.ymgme.2021.03.003","article-title":"Bloom syndrome and the underlying causes of genetic instability","volume":"133","author":"Ababou","year":"2021","journal-title":"Mol Genet Metab"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1086\/302616","article-title":"Transfection of BLM into cultured bloom syndrome cells reduces the sister-chromatid exchange rate toward normal","volume":"65","author":"Ellis","year":"1999","journal-title":"Am J Hum Genet"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.3390\/genes7090069","article-title":"Regulation of BLM nucleolar localization","volume":"7","author":"Tangeman","year":"2016","journal-title":"Genes"},{"key":"B83","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1186\/s13148-021-01160-z","article-title":"Targeting the methyltransferase SETD8 impairs tumor cell survival and overcomes drug resistance independently of p53 status in multiple myeloma","volume":"13","author":"Herviou","year":"2021","journal-title":"Clin Epigenet"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.08689.x","article-title":"Lenalidomide downregulates the cell survival factor, interferon regulatory factor-4, providing a potential mechanistic link for predicting response: Lenalidomide downregulates IRF4","volume":"154","author":"Lopez-Girona","year":"2011","journal-title":"Br J Haematol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.10.5858","article-title":"DNA Double-stranded breaks induce histone H2AX phosphorylation on serine 139","volume":"273","author":"Rogakou","year":"1998","journal-title":"J Biol Chem"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00610-2","article-title":"A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage","volume":"10","author":"Paull","year":"2000","journal-title":"Curr Biol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100569200","article-title":"Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress","volume":"276","author":"Ward","year":"2001","journal-title":"J Biol Chem"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300198200","article-title":"Phosphorylation of histone H2AX and activation of Mre11, Rad50, and Nbs1 in response to replication-dependent DNA double-strand breaks induced by mammalian DNA topoisomerase I cleavage complexes","volume":"278","author":"Furuta","year":"2003","journal-title":"J Biol Chem"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.09.038","article-title":"MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks","volume":"123","author":"Stucki","year":"2005","journal-title":"Cell"},{"key":"B90","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/j.cell.2007.09.040","article-title":"RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins","volume":"131","author":"Mailand","year":"2007","journal-title":"Cell"},{"key":"B91","article-title":"Specific proteolytic cleavage of poly(ADP-ribose) polymerase: An early marker of chemotherapy-induced apoptosis","volume":"53","author":"Kaufmann","year":"1993","journal-title":"Cancer Res"},{"key":"B92","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1038\/s41467-020-15740-9","article-title":"Timing the initiation of multiple myeloma","volume":"11","author":"Rustad","year":"2020","journal-title":"Nat Commun"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2021.279360","article-title":"Comprehensive genomic analysis of refractory multiple myeloma reveals a complex mutational landscape associated with drug resistance and novel therapeutic vulnerabilities","volume":"107","author":"Giesen","year":"2022","journal-title":"Haematologica"},{"key":"B94","doi-asserted-by":"publisher","first-page":"3617","DOI":"10.1038\/s41467-020-17459-z","article-title":"Accelerated single cell seeding in relapsed multiple myeloma","volume":"11","author":"Landau","year":"2020","journal-title":"Nat Commun"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003541","article-title":"Comprehensive CRISPR-Cas9 screens identify genetic determinants of drug responsiveness in multiple myeloma","volume":"5","author":"Bohl","year":"2021","journal-title":"Blood Adv"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2022.146581","article-title":"Role of the TATA-box binding protein (TBP) and associated family members in transcription regulation","volume":"833","author":"Mishal","year":"2022","journal-title":"Gene"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210605","article-title":"Orchestration of chromatin-based processes: Mind the TRRAP","volume":"26","author":"Murr","year":"2007","journal-title":"Oncogene"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1343","article-title":"Histone acetylation by trrap\u2013Tip60 modulates loading of repair proteins and repair of DNA double-strand breaks","volume":"8","author":"Murr","year":"2006","journal-title":"Nat Cell Biol"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11100988","article-title":"RNA-Sequencing-Based transcriptomic score with prognostic and theranostic values in multiple myeloma","volume":"11","author":"Alaterre","year":"2021","journal-title":"JPM"},{"key":"B100","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1515\/bmc-2014-0027","article-title":"C-terminal binding proteins: Central players in development and disease","volume":"5","author":"Stankiewicz","year":"2014","journal-title":"Biomol Concepts"},{"key":"B101","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.ctrv.2018.09.001","article-title":"Drug resistance in multiple myeloma","volume":"70","author":"Robak","year":"2018","journal-title":"Cancer Treat Rev"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11040439","article-title":"Antioxidant defenses confer resistance to high dose melphalan in multiple myeloma cells","volume":"11","author":"Gourzones","year":"2019","journal-title":"Cancers"},{"key":"B103","doi-asserted-by":"publisher","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"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2014.2726","article-title":"PJ34, a poly(ADP-ribose) polymerase (PARP) inhibitor, reverses melphalan-resistance and inhibits repair of DNA double-strand breaks by targeting the FA\/BRCA pathway in multidrug resistant multiple myeloma cell line RPMI8226\/R","volume":"46","author":"Xiong","year":"2015","journal-title":"Int J Oncol"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2020.03.008","article-title":"PARP inhibition synergizes with melphalan but does not reverse resistance completely","volume":"26","author":"Patel","year":"2020","journal-title":"Biol Blood Marrow Transplant"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2015.1040951","article-title":"A peptide nucleic acid targeting nuclear RAD51 sensitizes multiple myeloma cells to melphalan treatment","volume":"16","author":"Alagpulinsa","year":"2015","journal-title":"Cancer Biol Ther"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.634789","article-title":"Functions of BLM helicase in cells: Is it acting like a double-edged sword","volume":"12","author":"Kaur","year":"2021","journal-title":"Front Genet"},{"key":"B108","doi-asserted-by":"publisher","first-page":"12377","DOI":"10.1038\/s41598-020-69033-8","article-title":"Investigating the pathogenic SNPs in BLM helicase and their biological consequences by computational approach","volume":"10","author":"Alzahrani","year":"2020","journal-title":"Sci Rep"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.2001.1874","article-title":"The distribution and expression of the bloom\u2019s syndrome gene product in normal and neoplastic human cells","volume":"85","author":"Turley","year":"2001","journal-title":"Br J Cancer"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1404807111","article-title":"Regulation of gene expression by the BLM helicase correlates with the presence of G-quadruplex DNA motifs","volume":"111","author":"Nguyen","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"B111","doi-asserted-by":"publisher","first-page":"e1133","DOI":"10.1002\/mgg3.1133","article-title":"Gene expression profile suggesting immunological dysregulation in two Brazilian bloom\u2019s syndrome cases","volume":"8","author":"Montenegro","year":"2020","journal-title":"Mol Genet Genom Med"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr545","article-title":"BLM helicase facilitates RNA polymerase I-mediated ribosomal RNA transcription","volume":"21","author":"Grierson","year":"2012","journal-title":"Hum Mol Genet"},{"key":"B113","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.mrfmmm.2012.12.002","article-title":"Collaborating functions of BLM and DNA topoisomerase I in regulating human rDNA transcription","author":"Grierson","year":"2013","journal-title":"Mutat Res\/Fundam Mol Mech Mutagen"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1016\/j.acthis.2017.01.009","article-title":"Ribosome biogenesis and cancer","volume":"119","author":"Derenzini","year":"2017","journal-title":"Acta Histochem"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.20892\/j.issn.2095-3941.2021.0178","article-title":"BLM helicase inhibition synergizes with PARP inhibition to improve the radiosensitivity of olaparib resistant non-small cell lung cancer cells by inhibiting homologous recombination repair","volume":"19","author":"Kong","year":"2022","journal-title":"Cancer Biol Med"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1186\/s41021-016-0037-9","article-title":"Mechanisms of interstrand DNA crosslink repair and human disorders","volume":"38","author":"Hashimoto","year":"2016","journal-title":"Genes Environ"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2017.1349102","article-title":"Melphalan hydrochloride for the treatment of multiple myeloma","volume":"18","author":"Esma","year":"2017","journal-title":"Expert Opin Pharmacother"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58321","article-title":"Molecular pathogenesis and clinical management of fanconi anemia","volume":"122","author":"Kee","year":"2012","journal-title":"J Clin Invest"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1038\/nature11863","article-title":"Fanconi anaemia and the repair of Watson and crick DNA crosslinks","volume":"493","author":"Kottemann","year":"2013","journal-title":"Nature"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.10.3417-3426.2003","article-title":"A multiprotein nuclear complex connects fanconi anemia and bloom syndrome","volume":"23","author":"Meetei","year":"2003","journal-title":"Mol Cell Biol"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2159","article-title":"Emergence of a DNA-damage response network consisting of fanconi anaemia and BRCA proteins","volume":"8","author":"Wang","year":"2007","journal-title":"Nat Rev Genet"},{"key":"B122","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.tig.2011.09.003","article-title":"Fanconi anemia and bloom\u2019s syndrome crosstalk through FANCJ\u2013BLM helicase interaction","volume":"28","author":"Suhasini","year":"2012","journal-title":"Trends Genet"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.12.006","article-title":"FANCM connects the genome instability disorders bloom\u2019s syndrome and fanconi anemia","volume":"36","author":"Deans","year":"2009","journal-title":"Mol Cell"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8707","article-title":"BLM promotes the activation of fanconi anemia signaling pathway","volume":"7","author":"Panneerselvam","year":"2016","journal-title":"Oncotarget"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks353","article-title":"RI-1: a chemical inhibitor of RAD51 that disrupts homologous recombination in human cells","volume":"40","author":"Budke","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006423108","article-title":"Inhibition of helicase activity by a small molecule impairs Werner syndrome helicase (WRN) function in the cellular response to DNA damage or replication stress","volume":"108","author":"Aggarwal","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1102-x","article-title":"WRN helicase is a synthetic lethal target in microsatellite unstable cancers","volume":"568","author":"Chan","year":"2019","journal-title":"Nature"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2020.09.001","article-title":"Synthetic lethal interactions of RECQ helicases","volume":"7","author":"Datta","year":"2021","journal-title":"Trends Cancer"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2019.02.006","article-title":"Werner Syndrome helicase is required for the survival of cancer cells with microsatellite instability","volume":"13","author":"Kategaya","year":"2019","journal-title":"iScience"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3891","article-title":"Therapeutic opportunities within the DNA damage response","volume":"15","author":"Pearl","year":"2015","journal-title":"Nat Rev Cancer"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b00083","article-title":"Discovery of isaindigotone derivatives as novel bloom\u2019s syndrome protein (BLM) helicase inhibitors that disrupt the BLM\/DNA interactions and regulate the homologous recombination repair","volume":"62","author":"Yin","year":"2019","journal-title":"J Med Chem"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00917","article-title":"Design, synthesis, and evaluation of new quinazolinone derivatives that inhibit bloom syndrome protein (BLM) helicase, trigger DNA damage at the telomere region, and synergize with PARP inhibitors","volume":"63","author":"Wang","year":"2020","journal-title":"J Med Chem"},{"key":"B133","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1186\/s12885-019-6146-7","article-title":"Screening antiproliferative drug for breast cancer from bisbenzylisoquinoline alkaloid tetrandrine and fangchinoline derivatives by targeting BLM helicase","volume":"19","author":"Zhang","year":"2019","journal-title":"BMC Cancer"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.65339","article-title":"Uncovering an allosteric mode of action for a selective inhibitor of human bloom syndrome protein","volume":"10","author":"Chen","year":"2021","journal-title":"eLife"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00861","article-title":"Treatment may be harmful: Mechanisms\/Prediction\/Prevention of drug-induced DNA damage and repair in multiple myeloma","volume":"10","author":"Gourzones","year":"2019","journal-title":"Front Genet"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.983181\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T07:14:17Z","timestamp":1670570057000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.983181\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,9]]},"references-count":135,"alternative-id":["10.3389\/fimmu.2022.983181"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.983181","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,9]]},"article-number":"983181"}}