Ana Pilar Gonzalez-Rodriguez

Detected variants passing all filters categorized as pathogenic or likely pathogenic somatic mutations.

Quality control of the 555 NGS samples included in the study.

Hematologic toxicity during treatment observed in patients enrolled in the GEM2012MENOS65, GEM-CLARIDEX and GEM-CESAR clinical trials compared to mutant HPC detected at baseline. P-value is calculated using corrected χ2 test.

Clinical and tumor microenvironmental characteristics of untreated, newly diagnosed active MM patients having normal (n = 129) vs mutant HPC (n = 38). P-value is calculated using corrected χ2 for dichotomous variables, and Kruskal-Wallis for numerical variables.

Genetic relationship between mutant HPC and tumor cells. Concordance between the mutational landscape of hematopoietic progenitor cells (HPC) and patient-paired tumor cells (n = 42) used as filtering criteria for mutations observed in RAS genes. All mutated genes in HPC are shown, whereas in tumor cells only the genes that were mutated and were mapped in the myeloid gene panel are shown. Samples were collected at different moments of treatment: in untreated patients (i.e., at diagnosis), after induction, intensification, or end of treatment (EoT). Cytogenetic alterations were determined by FISH during diagnostic procedures. HPC and tumor cell illustrations were created with BioRender.com.

Mutational landscape of HPC according to a variant allele frequency (VAF) ≥2% among untreated patients with MM. Frequencies are calculated according to all patients with BM HPC at diagnosis (n = 232).

Overview illustrating a graphical representation of gating strategy used to detect bone marrow CD34+ hematopoietic progenitor cells (HPC) and plasma cells (PCs) using fluorescence activated cell sorting (BD FACSDiva v 8.0.2). Panels show bivariate dot plots representations in which HPC were gated using conventional manual analysis strategy.

Key disease characteristics between patients with available (n = 308) and unavailable (n = 583) samples included and not included in this study from the GEM2012MENOS65, GEM-CESAR, and GEM-CLARIDEX trials. P-value is calculated using corrected χ2 for dichotomous variables, and Kruskal-Wallis for numerical variables.