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Applying Clonal Competition Assays (CCA)\u00a0by\u00a0co\u2010culturing color\u2010labeled genetically modified cell models, we recently showed that mono\u2010 and biallelic alterations in\n                    <jats:italic>TP53<\/jats:italic>\n                    transmit a fitness advantage to the cells. Here, we report a similar dynamic for two mutations in\n                    <jats:italic>KRAS<\/jats:italic>\n                    (G12A and A146T), providing a biological rationale for the high frequency of\n                    <jats:italic>KRAS<\/jats:italic>\n                    and\n                    <jats:italic>TP53<\/jats:italic>\n                    alterations at MM relapse. Resistance mutations, on the other hand, did not endow MM cells with a general fitness advantage but rather presented a disadvantage compared to the wild\u2010type.\n                    <jats:italic>CUL4B<\/jats:italic>\n                    KO and\n                    <jats:italic>IKZF1<\/jats:italic>\n                    A152T transmit resistance against immunomodulatory agents,\n                    <jats:italic>PSMB5<\/jats:italic>\n                    A20T to proteasome inhibition. However, MM cells harboring such lesions only outcompete the culture in the presence of the respective drug. To better prevent the selection of clones with the potential of inducing relapse, these results argue in favor of treatment\u2010free breaks or a switch of the drug class given as maintenance therapy. In summary, the fitness benefit of\n                    <jats:italic>TP53<\/jats:italic>\n                    and\n                    <jats:italic>KRAS<\/jats:italic>\n                    mutations was not treatment\u2010related, unlike patient\u2010derived drug resistance alterations that may only induce an advantage under treatment. CCAs are suitable models for the study of clonal evolution and competitive (dis)advantages conveyed by a specific genetic lesion of interest, and their dependence on external factors such as the treatment.\n                  <\/jats:p>","DOI":"10.1002\/hem3.110","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T03:34:48Z","timestamp":1720668888000},"source":"Crossref","is-referenced-by-count":6,"title":["Clonal competition assays identify fitness signatures in cancer progression and resistance in multiple myeloma"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3927-9163","authenticated-orcid":false,"given":"Larissa","family":"Haertle","sequence":"first","affiliation":[{"name":"Department of Internal Medicine II University Hospital W\u00fcrzburg W\u00fcrzburg Germany"},{"name":"Department of Hematology Hospital Universitario 12 de Octubre, Spanish National Cancer Research Center (CNIO), Complutense University Madrid Madrid Spain"},{"name":"Department of Medicine III, Klinikum rechts der Isar Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umair","family":"Munawar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II University Hospital W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hip\u00f3lito N. 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Internal Medicine II University Hospital W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Vogt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II University Hospital W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Bischler","sequence":"additional","affiliation":[{"name":"Core Unit Systems Medicine University of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula L.","family":"del Campo","sequence":"additional","affiliation":[{"name":"Department of Hematology Hospital Universitario 12 de Octubre, Spanish National Cancer Research Center (CNIO), Complutense University Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungbin","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II 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