ADAR1 overexpression is an independent prognostic marker. (A) Analysis of ADAR1 expression in publicly available MM patient data sets from Italian GSE13591 (n = 158) and Mayo Clinic (n = 162). Average (avg) intensity of the GEP probe of each patient group is stated on the graphs, with their standard deviation (sd). (B) ADAR1 mRNA expression from the whole-transcriptome sequencing of our in-house primary patient samples (n = 17) on the Illumina Hi-Seq 4000 platform. The mean expression (Ave) ± sd for each cohort is stated in the table below the graph. (C) Immunofluorescence analysis of ADAR1 expression in bone marrow tissue microarray (left, L), with corresponding segmented image masks (right, R). CD138 marks plasma cells. Percentage of double positivity (CD138⁺/ADAR1⁺) is indicated below the images. Color coding is stated on the figure. Dot plot on the right is the quantification of the immunofluorescence analysis of ADAR1 protein expression on the TMA. ADAR1 positivity refers to the double-positive staining for both anti-CD138 and anti-ADAR1. (D) qPCR analysis of ADAR1 mRNA expression of primary samples (from healthy donors and patients with MM) and MM cell lines. Relative expression was calculated with ddCt method normalizing to GAPDH expression. (E) GEP analysis of ADAR1 expression in patients enrolled into Mayo Clinic and University of Arkansas for Medical Sciences (UAMS) clinical trial based on different translocation/cyclin D (TC) classification. (F) Kaplan-Meier curve demonstrating the overall survival of patients (from different MM data sets; namely, Assessment of Proteasome Inhibition for Extending Remissions [APEX] and UAMS) with differential ADAR1 expression. CI, confidence interval; HR, hazard ratio; HV, healthy volunteer; MGUS, monoclonal gammopathy of undetermined significance; MM, multiple myeloma; ND, newly diagnosed; PCL, plasma cell leukemia; R, relapsed; SMM, smoldering multiple myeloma.