Fig. 3: A common MAPK–MYC axis dictates multiple myeloma progression.
a, Quantification of the TMB, which corresponds to the total number of somatic mutations per tumor, according to WES analysis (left). Distribution of mutations in genes within signaling and cancer-related pathways in MM (n = 62) and MGUS (n = 3) primary samples, and in MM-derived cell lines (n = 6). Kruskal–Wallis test P values adjusted for multiple comparisons by Dunn’s test are indicated. b, Quantification of copy number variation and TMB according to WES data from MM cells from Trp53-BIcγ1 mice compared with the remaining strains, and in MM patients from the CoMMpass study with and without 17p/TP53 deletion and/or TP53 somatic mutations. Mann–Whitney test two-tailed P values are indicated. c, Western blot analyses revealed ERK phosphorylation in mouse and human MM cell lines. The mouse cell line 5TGM1 was included as a positive control. d, The MEK inhibitor trametinib induced a dose-dependent reduction in ERK phosphorylation in mouse and human MM-derived cell lines. e, Dose-dependent decrease in viability of mouse and human MM cell lines following trametinib treatment. Data corresponding to the mean ± s.e.m. from two to ten independent experiments are represented for each cell line. f, Reduced phosphorylation of MYC at S62 (pMYC-S62) following treatment with trametinib in mouse and human MM cell lines. Quantification of the fold change in expression levels of pMYC-S62 with respect to total MYC protein is shown. Boxes represent the median, upper and lower quartiles and whiskers represent minimum to maximum range (a and b). **P < 0.01; ***P < 0.001.
