{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:36Z","timestamp":1787027796062,"version":"build-2736575974"},"reference-count":107,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T00:00:00Z","timestamp":1627862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Multiple myeloma (MM) is a blood cancer characterized by the accumulation of malignant monoclonal plasma cells in the bone marrow. It develops through a series of premalignant plasma cell dyscrasia stages, most notable of which is the Monoclonal Gammopathy of Undetermined Significance (MGUS). Significant advances have been achieved in uncovering the genomic aberrancies underlying the pathogenesis of MGUS-MM. In this review, we discuss in-depth the genomic evolution of MM and focus on the prognostic implications of the accompanied molecular and cytogenetic aberrations. We also dive into the latest investigatory techniques used for the diagnoses and risk stratification of MM patients.<\/jats:p>","DOI":"10.3390\/cells10081961","type":"journal-article","created":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T08:44:11Z","timestamp":1627893851000},"page":"1961","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["A Comprehensive Review of the Genomics of Multiple Myeloma: Evolutionary Trajectories, Gene Expression Profiling, and Emerging Therapeutics"],"prefix":"10.3390","volume":"10","author":[{"given":"Hassan","family":"Awada","sequence":"first","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7636-8907","authenticated-orcid":false,"given":"Bicky","family":"Thapa","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1445-7947","authenticated-orcid":false,"given":"Hussein","family":"Awada","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Dong","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6829-5544","authenticated-orcid":false,"given":"Carmelo","family":"Gurnari","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parameswaran","family":"Hari","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binod","family":"Dhakal","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,2]]},"reference":[{"key":"ref_1","unstructured":"(2021, May 07). SEER Cancer Statistics Review. 1975\u20132017. SEER, Available online: https:\/\/seer.cancer.gov\/csr\/1975_2017\/index.html."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/leu.2017.211","article-title":"Bortezomib before and after high-dose therapy in myeloma: Long-term results from the phase III HOVON-65\/GMMG-HD4 trial","volume":"32","author":"Goldschmidt","year":"2018","journal-title":"Leukemia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1182\/bloodadvances.2019000524","article-title":"Long-term outcomes after autologous stem cell transplantation for multiple myeloma","volume":"4","author":"Nishimura","year":"2020","journal-title":"Blood Adv."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1122","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":"ref_5","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1038\/leu.2016.380","article-title":"Trends in overall survival and costs of multiple myeloma, 2000\u20132014","volume":"31","author":"Fonseca","year":"2017","journal-title":"Leukemia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.gde.2015.03.008","article-title":"Genomic heterogeneity in multiple myeloma","volume":"30","author":"Szalat","year":"2015","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1056\/NEJMoa01133202","article-title":"A Long-Term Study of Prognosis in Monoclonal Gammopathy of Undetermined Significance","volume":"346","author":"Yle","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_8","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."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1182\/blood-2012-01-405985","article-title":"Clonal competition with alternating dominance in multiple myeloma","volume":"120","author":"Keats","year":"2012","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1182\/blood-2012-03-412981","article-title":"Intraclonal heterogeneity and distinct molecular mechanisms characterize the development of t(4;14) and t(11;14) myeloma","volume":"120","author":"Walker","year":"2012","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1060","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":"ref_12","doi-asserted-by":"crossref","first-page":"101153","DOI":"10.1016\/j.beha.2020.101153","article-title":"Genomic profiling of multiple myeloma: New insights and modern technologies","volume":"33","author":"Hultcrantz","year":"2020","journal-title":"Best Pr. Res. Clin. Haematol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5434","DOI":"10.1158\/1078-0432.CCR-16-0867","article-title":"Gene Expression Profiles in Myeloma: Ready for the Real World?","volume":"22","author":"Szalat","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41408-020-00348-5","article-title":"Cytogenetic abnormalities in multiple myeloma: Association with disease characteristics and treatment response","volume":"10","author":"Abdallah","year":"2020","journal-title":"Blood Cancer J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/864058","article-title":"The Genetic Architecture of Multiple Myeloma","volume":"2014","author":"Prideaux","year":"2014","journal-title":"Adv. Hematol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.3324\/haematol.2010.024778","article-title":"Identification of translocation products but not K-RAS mutations in memory B cells from patients with multiple myeloma","volume":"95","author":"Rasmussen","year":"2010","journal-title":"Haematologica"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5412","DOI":"10.1182\/blood-2008-12-194241","article-title":"Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: A prospective study","volume":"113","author":"Landgren","year":"2009","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e538","DOI":"10.1016\/S1470-2045(14)70442-5","article-title":"International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma","volume":"15","author":"Rajkumar","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1101\/gr.265520.120","article-title":"Chromatin activation as a unifying principle underlying pathogenic mechanisms in multiple myeloma","volume":"30","author":"Kulis","year":"2020","journal-title":"Genome Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/ejh.12892","article-title":"Genomewide association study on monoclonal gammopathy of unknown significance (MGUS)","volume":"99","author":"Thomsen","year":"2017","journal-title":"Eur. J. Haematol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/ng.993","article-title":"Common variation at 3p22.1 and 7p15.3 influences multiple myeloma risk","volume":"44","author":"Broderick","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1038\/leu.2016.199","article-title":"HLA polymorphism and risk of multiple myeloma","volume":"30","author":"Beksac","year":"2016","journal-title":"Leukemia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6026","DOI":"10.1158\/1078-0432.CCR-07-0031","article-title":"Hyperdiploidy Is a Common Finding in Monoclonal Gammopathy of Undetermined Significance and Monosomy 13 Is Restricted to These Hyperdiploid Patients","volume":"13","author":"Brousseau","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1182\/blood-2005-02-0761","article-title":"A validated FISH trisomy index demonstrates the hyperdiploid and nonhyperdiploid dichotomy in MGUS","volume":"106","author":"Chng","year":"2005","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/sj.leu.2403555","article-title":"Genetic heterogeneity in multiple myeloma","volume":"19","author":"Magrangeas","year":"2004","journal-title":"Leukemia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1182\/blood-2011-11-390658","article-title":"Trisomies in multiple myeloma: Impact on survival in patients with high-risk cytogenetics","volume":"119","author":"Kumar","year":"2012","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.beha.2007.08.004","article-title":"Genetic events in the pathogenesis of multiple myeloma","volume":"20","author":"Chng","year":"2007","journal-title":"Best Pr. Res. Clin. Haematol."},{"key":"ref_28","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"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nrc746","article-title":"Multiple myeloma: Evolving genetic events and host interactions","volume":"2","author":"Kuehl","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1002\/1097-0142(19931001)72:7<2148::AID-CNCR2820720714>3.0.CO;2-Q","article-title":"Antigenic stimulation and multiple myeloma. A prospective study","volume":"72","author":"Bourguet","year":"1993","journal-title":"Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1038\/sj.leu.2404229","article-title":"Inflammation and multiple myeloma: The Toll connection","volume":"20","author":"Mantovani","year":"2006","journal-title":"Leukemia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-39672-7","article-title":"Toll-Like Receptor 4 Activation Promotes Multiple Myeloma Cell Growth and Survival Via Suppression of The Endoplasmic Reticulum Stress Factor Chop","volume":"9","author":"Bagratuni","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3880","DOI":"10.1182\/blood.V96.12.3880","article-title":"The interleukin-6 receptor alpha-chain (CD126) is expressed by neoplastic but not normal plasma cells","volume":"96","author":"Rawstron","year":"2000","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1046\/j.1365-2141.1999.01705.x","article-title":"Mcl-1 and Bcl-xL are co-regulated by IL-6 in human myeloma cells","volume":"107","author":"Puthier","year":"1999","journal-title":"Br. J. Haematol."},{"key":"ref_35","first-page":"S63","article-title":"The screening imperative for multiple myeloma","volume":"587","author":"Rajkumar","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41408-021-00406-6","article-title":"Prognosis of young patients with monoclonal gammopathy of undetermined significance (MGUS)","volume":"11","author":"Pang","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1001\/jamaoncol.2019.1568","article-title":"Association of Immune Marker Changes with Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma","volume":"5","author":"Landgren","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1093\/jncimonographs\/lgn011","article-title":"Characterization of MYC Translocations in Multiple Myeloma Cell Lines","volume":"2008","author":"Dib","year":"2008","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_39","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"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3082","DOI":"10.1182\/blood.V98.10.3082","article-title":"Rearrangements of the c-myc oncogene are present in 15% of primary human multiple myeloma tumors","volume":"98","author":"Gerson","year":"2001","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1002\/gcc.20563","article-title":"Secondary genomic rearrangements involving immunoglobulin or MYC loci show similar prevalences in hyperdiploid and nonhyperdiploid myeloma tumors","volume":"47","author":"Gabrea","year":"2008","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6581","DOI":"10.1158\/1078-0432.CCR-20-2283","article-title":"Implications of MYC Rearrangements in Newly Diagnosed Multiple Myeloma","volume":"26","author":"Abdallah","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4235","DOI":"10.1182\/blood-2007-10-119123","article-title":"An analysis of the clinical and biologic significance of TP53 loss and the identification of potential novel transcriptional targets of TP53 in multiple myeloma","volume":"112","author":"Xiong","year":"2008","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.3324\/haematol.2010.023697","article-title":"Mutations in TP53 are exclusively associated with del(17p) in multiple myeloma","volume":"95","author":"Eveillard","year":"2010","journal-title":"Haematologica"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1158\/0008-5472.CAN-03-2876","article-title":"Genetics and Cytogenetics of Multiple Myeloma","volume":"64","author":"Fonseca","year":"2004","journal-title":"Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/j.1365-2141.2004.05199.x","article-title":"Multiple myeloma involving central nervous system: High frequency of chromosome 17p13.1 (p53) deletions","volume":"127","author":"Chang","year":"2004","journal-title":"Br. J. Haematol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1182\/blood-2018-10-880831","article-title":"High subclonal fraction of 17p deletion is associated with poor prognosis in multiple myeloma","volume":"133","author":"Thakurta","year":"2019","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1182\/blood.V98.5.1555","article-title":"Detection of N-Ras codon 61 mutations in subpopulations of tumor cells in multiple myeloma at presentation","volume":"98","author":"Kalakonda","year":"2001","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1038\/leu.2008.142","article-title":"Clinical and biological significance of RAS mutations in multiple myeloma","volume":"22","author":"Chng","year":"2008","journal-title":"Leukemia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1182\/blood-2013-05-504340","article-title":"Mutation of NRAS but not KRAS significantly reduces myeloma sensitivity to single-agent bortezomib therapy","volume":"123","author":"Mulligan","year":"2014","journal-title":"Blood"},{"key":"ref_51","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-\u03baB Pathways by Diverse Genetic Abnormalities in Multiple Myeloma","volume":"12","author":"Annunziata","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"59","DOI":"10.18632\/oncotarget.109","article-title":"A critical role for the NFkB pathway in multiple myeloma","volume":"1","author":"Demchenko","year":"2010","journal-title":"Oncotarget"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ccr.2007.07.003","article-title":"Promiscuous Mutations Activate the Noncanonical NF-\u03baB Pathway in Multiple Myeloma","volume":"12","author":"Keats","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/sj.leu.2402328","article-title":"Frequent inactivation of the cyclin-dependent kinase inhibitor p18 by homozygous deletion in multiple myeloma cell lines: Ectopic p18 expression inhibits growth and induces apoptosis","volume":"16","author":"Kulkarni","year":"2002","journal-title":"Leukemia"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1006\/cimm.1995.1076","article-title":"Interleukin-6 Inhibits Apoptosis of Malignant Plasma Cells","volume":"162","author":"Lichtenstein","year":"1995","journal-title":"Cell. Immunol."},{"key":"ref_56","first-page":"1282","article-title":"Bcl-2 protein expression is not related to short survival in multiple myeloma","volume":"9","author":"Ong","year":"1995","journal-title":"Leukemia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4266","DOI":"10.1182\/blood.V90.11.4266","article-title":"Mutations in the Fas antigen in patients with multiple myeloma","volume":"90","author":"Landowski","year":"1997","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1182\/blood.V89.7.2500","article-title":"Frequent Hypermethylation of p16 and p15 Genes in Multiple Myeloma","volume":"89","author":"Ng","year":"1997","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1038\/leu.2009.174","article-title":"International Myeloma Working Group molecular classification of multiple myeloma: Spotlight review","volume":"23","author":"Fonseca","year":"2009","journal-title":"Leukemia"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"625","DOI":"10.5858\/arpa.2012-0209-OA","article-title":"Plasma Cell Enrichment Enhances Detection of High-Risk Cytogenomic Abnormalities by Fluorescence In Situ Hybridization and Improves Risk Stratification of Patients with Plasma Cell Neoplasms","volume":"137","author":"Lu","year":"2013","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.cancergencyto.2008.11.007","article-title":"Interphase FISH in plasma cell dyscrasia: Increase in abnormality detection with plasma cell enrichment","volume":"189","author":"Pozdnyakova","year":"2009","journal-title":"Cancer Genet. Cytogenet."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ma, E.S.K., Wang, C.L.N., Wong, A.T.C., Choy, G., and Chan, T.L. (2016). Target fluorescence in-situ hybridization (Target FISH) for plasma cell enrichment in myeloma. Mol. Cytogenet., 9.","DOI":"10.1186\/s13039-016-0263-7"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1200\/JCO.2015.61.2267","article-title":"Revised International Staging System for Multiple Myeloma: A Report from International Myeloma Working Group","volume":"33","author":"Palumbo","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1002\/ajh.25791","article-title":"Multiple myeloma: 2020 update on diagnosis, risk-stratification and management","volume":"95","author":"Rajkumar","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1200\/JCO.18.00776","article-title":"Development and Validation of a Cytogenetic Prognostic Index Predicting Survival in Multiple Myeloma","volume":"37","author":"Perrot","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41408-020-00359-2","article-title":"Multiple myeloma current treatment algorithms","volume":"10","author":"Rajkumar","year":"2020","journal-title":"Blood Cancer J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/s41375-018-0196-8","article-title":"A high-risk, Double-Hit, group of newly diagnosed myeloma identified by genomic analysis","volume":"33","author":"Walker","year":"2019","journal-title":"Leukemia"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-62885-0","article-title":"Concepts of Double Hit and Triple Hit Disease in Multiple Myeloma, Entity and Prognostic Significance","volume":"10","author":"Baysal","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_69","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"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/j.1349-7006.2003.tb01445.x","article-title":"Frequent occurrence of CCND1 deregulation in patients with early stages of plasma cell dyscrasia","volume":"94","author":"Miura","year":"2003","journal-title":"Cancer Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"6333","DOI":"10.1200\/JCO.2005.05.021","article-title":"Molecular Pathogenesis and a Consequent Classification of Multiple Myeloma","volume":"23","author":"Bergsagel","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2020","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":"ref_73","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1182\/blood-2009-12-261032","article-title":"Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients","volume":"116","author":"Broyl","year":"2010","journal-title":"Blood"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2276","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":"2006","journal-title":"Blood"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1038\/leu.2012.127","article-title":"A gene expression signature for high-risk multiple myeloma","volume":"26","author":"Kuiper","year":"2012","journal-title":"Leukemia"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4798","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":"J. Clin. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1158\/1078-0432.CCR-09-2831","article-title":"Homozygous Deletion Mapping in Myeloma Samples Identifies Genes and an Expression Signature Relevant to Pathogenesis and Outcome","volume":"16","author":"Dickens","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3177","DOI":"10.1182\/blood-2006-09-044974","article-title":"Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib","volume":"109","author":"Mulligan","year":"2006","journal-title":"Blood"},{"key":"ref_79","doi-asserted-by":"crossref","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":"2010","journal-title":"Haematologica"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1002\/hon.2848","article-title":"Sequencing of myeloma therapy: Finding the right path among many standards","volume":"39","author":"Rajkumar","year":"2021","journal-title":"Hematol. Oncol."},{"key":"ref_81","first-page":"467","article-title":"Initial genome sequencing and analysis of multiple myeloma","volume":"471","author":"Chapman","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2604","DOI":"10.1038\/s41375-018-0037-9","article-title":"Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups","volume":"32","author":"Bolli","year":"2018","journal-title":"Leukemia"},{"key":"ref_83","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"},{"key":"ref_84","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. Clin. Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1038\/s41375-018-0103-3","article-title":"Whole-genome sequencing of multiple myeloma reveals oncogenic pathways are targeted somatically through multiple mechanisms","volume":"32","author":"Hoang","year":"2018","journal-title":"Leukemia"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Sharma, N., Smadbeck, J.B., Abdallah, N., Zepeda-Mendoza, C., Binder, M., Pearce, K.E., Asmann, Y.W., Peterson, J.F., Ketterling, R.P., and Greipp, P.T. (2021). The prognostic role of MYC structural variants identified by NGS and FISH in multiple myeloma. Clin. Cancer Res.","DOI":"10.1158\/1078-0432.CCR-21-0005"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-11680-1","article-title":"Genomic landscape and chronological reconstruction of driver events in multiple myeloma","volume":"10","author":"Maura","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1038\/ncomms3997","article-title":"Heterogeneity of genomic evolution and mutational profiles in multiple myeloma","volume":"5","author":"Bolli","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1038\/s41375-019-0689-0","article-title":"Role of AID in the temporal pattern of acquisition of driver mutations in multiple myeloma","volume":"34","author":"Maura","year":"2020","journal-title":"Leukemia"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S1470-2045(12)70489-8","article-title":"Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: A randomised, multicentre, placebo-controlled, phase 2 study","volume":"14","author":"Shaw","year":"2013","journal-title":"Lancet Oncol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1200\/JCO.2007.14.4956","article-title":"Phase I Pharmacokinetic and Pharmacodynamic Study of the Oral, Small-Molecule Mitogen-Activated Protein Kinase Kinase 1\/2 Inhibitor AZD6244 (ARRY-142886) in Patients with Advanced Cancers","volume":"26","author":"Adjei","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1158\/2159-8290.CD-13-1038","article-title":"Efficacy of Intermittent Combined RAF and MEK Inhibition in a Patient with Concurrent BRAF- and NRAS-Mutant Malignancies","volume":"4","author":"Klimek","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1056\/NEJMoa1002011","article-title":"Inhibition of Mutated, Activated BRAF in Metastatic Melanoma","volume":"363","author":"Flaherty","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"7661","DOI":"10.1158\/0008-5472.CAN-06-1098","article-title":"A Novel Orally Active Small Molecule Potently Induces G1 Arrest in Primary Myeloma Cells and Prevents Tumor Growth by Specific Inhibition of Cyclin-Dependent Kinase 4\/6","volume":"66","author":"Baughn","year":"2006","journal-title":"Cancer Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1200\/JCO.2016.70.6705","article-title":"Genomics of Multiple Myeloma","volume":"35","author":"Cleynen","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/nature10762","article-title":"Clonal evolution in cancer","volume":"481","author":"Greaves","year":"2012","journal-title":"Nature"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1182\/blood-2012-06-430645","article-title":"Darwinian evolution and tiding clones in multiple myeloma","volume":"120","author":"Bahlis","year":"2012","journal-title":"Blood"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1007\/s12185-020-02829-6","article-title":"Molecular basis of clonal evolution in multiple myeloma","volume":"111","author":"Furukawa","year":"2020","journal-title":"Int. J. Hematol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1002\/hon.2586","article-title":"Multiple myeloma: Every year a new standard?","volume":"37","author":"Rajkumar","year":"2019","journal-title":"Hematol. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Cardona-Benavides, I.J., de Ram\u00f3n, C., and Guti\u00e9rrez, N.C. (2021). Genetic Abnormalities in Multiple Myeloma: Prognostic and Therapeutic Implications. Cells, 10.","DOI":"10.3390\/cells10020336"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.1182\/blood-2017-06-788786","article-title":"Efficacy of venetoclax as targeted therapy for relapsed\/refractory t(11;14) multiple myeloma","volume":"130","author":"Kumar","year":"2017","journal-title":"Blood"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1182\/blood-2017-06-788323","article-title":"Promising efficacy and acceptable safety of venetoclax plus bortezomib and dexamethasone in relapsed\/refractory MM","volume":"130","author":"Moreau","year":"2017","journal-title":"Blood"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/S1470-2045(20)30525-8","article-title":"Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): A randomised, double-blind, multicentre, phase 3 trial","volume":"21","author":"Kumar","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e196","DOI":"10.1016\/S2352-3026(16)00021-1","article-title":"Bromodomain inhibitor OTX015 in patients with lymphoma or multiple myeloma: A dose-escalation, open-label, pharmacokinetic, phase 1 study","volume":"3","author":"Amorim","year":"2016","journal-title":"Lancet Haematol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1182\/blood-2020-136980","article-title":"Early Pharmacodynamic Changes in T-Cell Activation, Proliferation, and Cytokine Production Confirm the Mode of Action of BFCR4350A, a FcRH5\/CD3 T-Cell-Engaging Bispecific Antibody, in Patients with Relapsed\/Refractory Multiple Myeloma","volume":"136","author":"Nakamura","year":"2020","journal-title":"Blood"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1182\/blood-2020-136985","article-title":"Initial Clinical Activity and Safety of BFCR4350A, a FcRH5\/CD3 T-Cell-Engaging Bispecific Antibody, in Relapsed\/Refractory Multiple Myeloma","volume":"136","author":"Cohen","year":"2020","journal-title":"Blood"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1200\/JCO.20.00223","article-title":"BiTEing the Tumor","volume":"38","author":"Kumar","year":"2020","journal-title":"J. Clin. Oncol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/8\/1961\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:38:57Z","timestamp":1760164737000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/8\/1961"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,2]]},"references-count":107,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["cells10081961"],"URL":"https:\/\/doi.org\/10.3390\/cells10081961","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,2]]}}}