Zhao et al. (2009) have demonstrated that loss of Smoothened (Smo), an important molecule of the Hh pathway, impairs HSC renewal and results in depletion of CML stem cells [29], although the effect of loss of Hh signaling through conditional deletion of Smo on adult hematopoiesis is still controversial [30,31]. This evidence concerns the gene SMO and chronic myelogenous leukemia, BCR-ABL1 positive.