More recently, two second generation autophagy inhibitors, Lys05 a highly potent lysosometric agent and PIK-III a selective inhibitor of VPS34, demonstrated synergistic effects with TKIs to reduce primary CML LSCs quiescence, compared to the first-generation autophagy inhibitor Hydroxychloroquine [33]. This evidence concerns the gene PIK3C3 and chronic myelogenous leukemia, BCR-ABL1 positive.