<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Chaidos, A.</style></author><author><style face="normal" font="default" size="100%">Barnes, C.P.</style></author><author><style face="normal" font="default" size="100%">Cowan, G.</style></author><author><style face="normal" font="default" size="100%">May, P.C.</style></author><author><style face="normal" font="default" size="100%">Melo, V.</style></author><author><style face="normal" font="default" size="100%">Hatjiharissi, E.</style></author><author><style face="normal" font="default" size="100%">Papaioannou, M.</style></author><author><style face="normal" font="default" size="100%">Harrington, H.</style></author><author><style face="normal" font="default" size="100%">Doolittle, H.</style></author><author><style face="normal" font="default" size="100%">Terpos, E.</style></author><author><style face="normal" font="default" size="100%">Dimopoulos, M.</style></author><author><style face="normal" font="default" size="100%">Abdalla, S.</style></author><author><style face="normal" font="default" size="100%">Yarranton, H.</style></author><author><style face="normal" font="default" size="100%">Naresh, K.</style></author><author><style face="normal" font="default" size="100%">Foroni, L.</style></author><author><style face="normal" font="default" size="100%">Reid, A.</style></author><author><style face="normal" font="default" size="100%">Rahemtulla, A.</style></author><author><style face="normal" font="default" size="100%">Stumpf, M.</style></author><author><style face="normal" font="default" size="100%">Roberts, I.</style></author><author><style face="normal" font="default" size="100%">Karadimitris, A.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Clinical drug resistance linked to interconvertible phenotypic and functional states of tumor-propagating cells in multiple myeloma</style></title><secondary-title><style face="normal" font="default" size="100%">Blood</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2013</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2013</style></date></pub-dates></dates><urls><web-urls><url><style face="normal" font="default" size="100%">https://www.scopus.com/inward/record.uri?eid=2-s2.0-84872345792&amp;doi=10.1182%2fblood-2012-06-436220&amp;partnerID=40&amp;md5=76c471635cfa1224fa76fb291b450b69</style></url></web-urls></urls><volume><style face="normal" font="default" size="100%">121</style></volume><pages><style face="normal" font="default" size="100%">318 - 328</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">The phenotype and function of cells enriched in tumor-propagating activity and their relationship to the phenotypic architecture in multiple myeloma (MM) are controversial. Here, in a cohort of 30 patients, we show that MM composes 4 hierarchically organized, clonally related subpopulations, which, although phenotypically distinct, share the same oncogenic chromosomal abnormalities as well as immunoglobulin heavy chain complementarity region 3 area sequence. Assessed in xenograft assays, myeloma-propagating activity is the exclusive property of a population characterized by its ability for bidirectional transition between the dominant CD19-CD138+ plasma cell (PC) and a low frequency CD19-CD138- subpopulation (termed Pre-PC); in addition, Pre-PCs are more quiescent and unlike PCs, are primarily localized at extramedullary sites. As shown by gene expression profiling, compared with PCs, Pre-PCs are enriched in epigenetic regulators, suggesting that epigenetic plasticity underpins the phenotypic diversification of myeloma-propagating cells. Prospective assessment in paired, pretreatment, and posttreatment bone marrow samples shows that Pre-PCs are up to 300-fold more drug-resistant than PCs. Thus, clinical drug resistance in MM is linked to reversible, bidirectional phenotypic transition of myeloma-propagating cells. These novel biologic insights have important clinical implications in relation to assessment of minimal residual disease and development of alternative therapeutic strategies in MM. © 2013 by The American Society of Hematology.</style></abstract><issue><style face="normal" font="default" size="100%">2</style></issue><notes><style face="normal" font="default" size="100%">Cited By :54Export Date: 21 February 2017</style></notes></record></records></xml>