In summary, we have used microarray-based gene expression analysis to show that global gene expression changes accompany BCR-ABL mutation acquisition in response to IM treatment, and that forced differentiation of CML cells with ATRA stimulates CD38 expression and blocks BCR-ABL mutation acquisition and CML cell relapse on IM in part through down regulation of NAD+ levels and SIRT1 activity. Here, ABL1 is linked to chronic myelogenous leukemia, BCR-ABL1 positive.