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In the disease state, bone healing is limited owing to increased osteoclastic and decreased osteoblastic activity, as well as an MM\u2010induced forward\u2010feedback cycle where bone\u2010embedded growth factors further enhance tumor progression as bone is resorbed. Recent work on somatic mutation in MM tumors has provided insight into cytogenetic changes associated with this disease; the initiating driver mutations causing MM are diverse because of the complexity and multitude of mutations inherent in MM tumor cells. This manuscript provides an overview of MM pathogenesis by summarizing cytogenic changes related to oncogenes and tumor suppressors associated with MM, reviewing risk factors, and describing the disease progression from monoclonal gammopathy of undetermined significance to overt MM. It also highlights the importance of the bone marrow microenvironment (BMM) in the establishment and progression of MM, as well as associated MM\u2010induced bone disease, and the relationship of the bone marrow to current and future therapeutics. This review highlights why understanding the basic biology of the healthy and diseased BMM is crucial in the quest for better treatments and work toward a cure for genetically diverse diseases such as MM.<\/jats:p>","DOI":"10.1111\/nyas.13038","type":"journal-article","created":{"date-parts":[[2016,3,22]],"date-time":"2016-03-22T17:05:31Z","timestamp":1458666331000},"page":"32-51","source":"Crossref","is-referenced-by-count":150,"title":["Multiple myeloma in the marrow: pathogenesis and treatments"],"prefix":"10.1111","volume":"1364","author":[{"given":"Heather","family":"Fairfield","sequence":"first","affiliation":[{"name":"Maine Medical Center Research Institute  Scarborough Maine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyne","family":"Falank","sequence":"additional","affiliation":[{"name":"Maine Medical Center Research Institute  Scarborough Maine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey","family":"Avery","sequence":"additional","affiliation":[{"name":"University of Maine  Orono Maine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela R.","family":"Reagan","sequence":"additional","affiliation":[{"name":"Maine Medical Center Research Institute  Scarborough Maine"},{"name":"University of Maine  Orono Maine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,3,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22718"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3257"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-07-0234"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2010.06.029"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66517"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2015.02.021"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-2212"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12239"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2010-0225"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1007"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-015-0837-0"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.5757.325-a"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1401337111"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-2280"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21166"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08207.x"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20006"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.112"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ede.0000172135.61188.2d"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60269-X"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/291546"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2014.63"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.025"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-09-380410"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.295"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.12.015"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404172"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2733"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-279596"},{"key":"e_1_2_9_31_1","first-page":"2997","article-title":"Decoding the pathophysiology and the genetics of multiple myeloma to identify new therapeutic targets","volume":"23","author":"Bergsagel P.L.","year":"2013","journal-title":"J. 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