biostudies-literatureHaertle LDeutsche ForschungsgemeinschaftInstituto de Salud Carlos IIIe110https://www.ebi.ac.uk/biostudies/studies/S-EPMC11237348biostudies-literatureUnknown8(7)Multiple myeloma (MM) is a genetically heterogeneous disease and the management of relapses is one of the biggest clinical challenges. <i>TP53</i> alterations are established high-risk markers and are included in the current disease staging criteria. <i>KRAS</i> is the most frequently mutated gene affecting around 20% of MM patients. Applying Clonal Competition Assays (CCA) by co-culturing color-labeled genetically modified cell models, we recently showed that mono- and biallelic alterations in <i>TP53</i> transmit a fitness advantage to the cells. Here, we report a similar dynamic for two mutations in <i>KRAS</i> (G12A and A146T), providing a biological rationale for the high frequency of <i>KRAS</i> and <i>TP53</i> alterations at MM relapse. Resistance mutations, on the other hand, did nHemaSphereClonal competition assays identify fitness signatures in cancer progression and resistance in multiple myeloma.PMC11237348FIS No. PI21/00314544189139Miguel Servet CP22/00082442740310493951700Muller NStuhmer TVogt CHernandez HNCSteinbrunn THoschle CHan SHeckel TBuenache NZhou XMunawar UBassermann FBarrio SMartin LRasche LBischler THaertle LMartin Kortum KArroyo-Barea ACuenca IDel Campo PLWaldschmidt JMartinez-Lopez JfalseClonal competition assays identify fitness signatures in cancer progression and resistance in multiple myeloma.Multiple myeloma (MM) is a genetically heterogeneous disease and the management of relapses is one of the biggest clinical challenges. <i>TP53</i> alterations are established high-risk markers and are included in the current disease staging criteria. <i>KRAS</i> is the most frequently mutated gene affecting around 20% of MM patients. Applying Clonal Competition Assays (CCA) by co-culturing color-labeled genetically modified cell models, we recently showed that mono- and biallelic alterations in <i>TP53</i> transmit a fitness advantage to the cells. Here, we report a similar dynamic for two mutations in <i>KRAS</i> (G12A and A146T), providing a biological rationale for the high frequency of <i>KRAS</i> and <i>TP53</i> alterations at MM relapse. Resistance mutations, on the other hand, did n2024-01-01T00:00:00Z2024 Jul2026-06-01T13:30:50.473Z2025-04-05T15:47:25.29ZS-EPMC112373483899372710.1002/hem3.110