Chronic myeloid leukemia (CML) is a hematopoietic stem cell (HSC) disorder with a constitutively activated tyrosine kinase, BCR-ABL fusion protein, arising from the reciprocal translocation between chromosomes 9 and 22. CML undergoes three serial processes, a chronic phase, an accelerated phase and a blast crisis phase. In the initiation of chronic phase, BCR-ABL fusion protein transforms normal HSC into leukemia initiating cells (LICs) in the bone marrow (BM). During the course, CML patients frequently developed remarkable basophilia in the BM and peripheral blood. We previously revealed that a chemokine, CCL3, was expressed by basophil-like leukemia cells present abundantly in CML BM and dampened normal HSC proliferation, thereby contributing to the maintenance of LICs in the BM at the initiating process of CML. Consistently, basophil depletion at the initiating process delayed CML progression. Here, we demonstrated that CML progression was delayed by a pharmacologic blockade of a CCL3 receptor, CCR5, at the initiation phase. On the contrary, CCR5 blockade did accelerate CML progression, when it was started after CML cells predominated in the BM. Moreover, the transplantation of CCR5-deficient mouse-derived LICs accelerated leukemogenesis together with augmented hepatomegaly, compared with that of WT mouse-derived LICs. Furthermore, enhanced leukemogenesis was associated with CML-derived common myeloid progenitor accumulation in spleen and liver but not BM. Given the fact that CML stem cells expressed CCR5 despite at a lesser level than normal HSCs, the present observations suggest that CCR5-mediated signals may have context-dependent diverse roles in CML pathogenesis.