Accumulated evidence has shown that oncogenic transformation of hematopoietic cells by BCR-ABL relies upon both its kinase and non-kinase activity.2 BCR-ABL activates multiple signaling pathways upon activation of its kinase activity, including PI3K-AKT, JAK/STAT, RAS/RAF/MEK/ERK, MYC and WNT/CTNNB1.3 Some genes, such as Alox5, Alox15, Scd1, and Blk,4,5 are essential for CML stem cells (LSC) survival and are activated by BCR-ABL independent of its kinase activity. The gene discussed is ABL1; the disease is chronic myelogenous leukemia, BCR-ABL1 positive.