In contrast, in the treatment group receiving AMD3100, FDA-approved Compound Library leukemic cell cluster regrowth was inhibited in the portal area . As a result, the macroscopic size of the liver and spleen in AMD3100-treated leukemic mice was smaller than that in control mice , and leukemic cell counts and organ volumes of the liver and spleen were significantly reduced . Interestingly, the largest decrease in leukemic cell count was observed in the liver of AMD3100-treated mice , and was seemingly correlated to the frequency of CXCR4-positive leukemic cells in each organ . During the long-term administration of AMD3100 or NS up to 60 days after AraC treatment, significantly fewer leukemic cells were present in the PB of AMD3100-treated mice compared with control mice receiving NS . Consequently, the control mice lost a significant amount of body weight, while the body weight of the AMD3100-treated mice was not significantly different compared with that of normal NOG mice . Furthermore, the AMD3100-treated mice demonstrated a higher overall survival, as estimated by the Kaplan-Meier method . Overall, these results strongly indicate that the SDF-1/CXCR4 signaling pathway plays a crucial role in re-expansion of ALL leukemic cells in the hepatic niche after chemotherapy and provide a novel anti-leukemic therapy that targets the extramedullary microenvironment. In this paper, we propose that leukemic extramedullary DAPT citations pathology is due to not only migrating, but also resident proliferating leukemic cells in the extramedullary niche. Using xeno-transplantation model, previous reports showed that human leukemic cells infiltrate the liver ; however, those reports lacked pathological or molecular assessment. Here, through the analysis of h-leukemic NOG model, we have demonstrated that hepatic extramedullary microenvironments provide a niche which harbors and propagates leukemic cells. We also demonstrated that the SDF-1/CXCR4 axis plays a crucial role in causing liver pathology. Recent studies revealed SDF- 1/CXCR4 axis involvement in the development and metastasis of solid tumor . This axis has also been known to play an indispensable role in the homing, proliferation, and survival of both normal hematopoietic and leukemic cells in the BM niche . In pediatric ALL patients, high expression of CXCR4 in leukemic cells was strongly predictive of extramedullary organ involvement , which is compatible with the findings in our murine xeno-transplantation model.