ROC curve for optimally predicting a kinase domain mutation by a rise in BCR-ABL RNA. The quantitative increase in BCR-ABL RNA levels was determined on 233 samples (from 132 patients) with a readable kinase domain (KD) DNA sequence, and a numeric BCR-ABL RNA level on both the sequenced sample and the immediately prior sample. Sensitivity was defined as the number of mutation-bearing samples with a transcript level rise above a moving (fold-change) cutoff threshold divided by the total number of samples with a mutation. Specificity was defined as the number of wild-type samples with a transcript level rise below the same cutoff threshold divided by the total number of samples without a mutation. The Youden index (J) is the vertical distance from each point on the receiver operating characteristic (ROC) curve to the diagonal “chance” line (from 0,0 to 1,1). The maximal J value (J_max, vertical dotted line), defining the optimal cutoff threshold (2.6-fold transcript level rise) for predicting a concomitant mutation, is denoted, as are the ROC points associated with a 2-, 3-, 5- and 10-fold transcript level rise.