p62/SQSTM1-dependent autophagic degradation of BCR-ABL in CML. Proposed model for the As₂O₃-dependent interaction of p62/SQSMT1 with BCR-ABL and subsequent autophagic degradation of BCR-ABL. The As₂O₃ treatment of CML cells triggers the interaction of p62 with BCR-ABL and the subsequent CTSB-mediated autophagic degradation of the fusion protein that is responsible for the antileukemic effect of the drug. The inhibition of autophagy by different means (pharmacologic agents or siRNA-mediated inhibition of Atg7, p62/SQSTM1, or CTSB) impairs BCR-ABL degradation and the effect of AS₂O₃, demonstrating the crucial role of autophagy in the effect of As₂O₃. Adapted from Figure 6 in the article by Goussetis et al that begins on page 3555.