Altered transforming growth factor beta-forkhead box signaling has also been found in LSCs following TKI exposure [29], with transforming growth factor beta inhibitors being effective in reducing colony formation in vitro [30], while a number of studies have implicated the Hedgehog pathway in LSC persistence 31, 32, 33 with consequent use of a smoothened (SMO) inhibitor, in combination with TKI, reducing CD34+ CP-CML cell engraftment in vivo [33]. This evidence concerns the gene CD34 and chronic myelogenous leukemia, BCR-ABL1 positive.