Apart from protection by the BMM, activation of signaling pathways such as WNT/β catenin, Hedgehog, PI3K, JAK/STAT in a BCR-ABL dependent and independent mechanisms guarantee CML LSCs persistence and elimination of these cells solely by TKIs seems ineffective [2,5,6]. This evidence concerns the gene ABL1 and chronic myelogenous leukemia, BCR-ABL1 positive.