BCR::ABL1 M244V and other N-lobe mutations are associated with resistance to asciminib. (A) Hematologic and molecular parameters of 4 patients with preexisting or rapidly emerging M244V substitutions. Dotted lines represent normal reference range for hematologic parameters. Dose (mg) and duration of TKI therapy is listed below each graph. BCR::ABL1 transcript levels were not assessed for patient 1, as this patient had never had an appreciable molecular response during 10 years of prior TKI therapy. (B) Normalized viability of Ba/F3 cells transduced with BCR::ABL1 isoforms depicted in increasing concentrations of asciminib after 48 hours of treatment. Data represent 3 independent experiments. Error bars represent standard error of the mean. EC50 values are represented in the table. (C) Representatives of 3 immunoblots of lysates of Ba/F3 cells expressing the isoforms listed in increasing concentrations of asciminib. Cells were lysed after 2 hours of asciminib exposure. GAPDH, glyceraldehyde-3-phosphate dehydrogenase; pSTAT5, phosphorylated STAT5.
