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Leukemia cell mobilization: a road to eradication?

Bone Marrow Transplantation volume 50, pages 905–906 (2015)Cite this article

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The interaction of a complex and highly regulated marrow microenvironment with hematopoietic stem cells (HSCs) is crucial for normal HSC survival and function. HSCs and AML blasts share many of the same surface molecules with adhesive properties that are critical for their retention in the marrow niche, where the microenvironment provides antiapoptotic and self-renewal signals and resistance to chemotherapy.1, 2, 3 The sanctuary provided by the marrow microenvironment is illustrated by the relative ease with which standard chemotherapy often clears leukemic cells from the peripheral blood relative to the marrow.

The chemokine receptor CXCR4 is expressed on normal HSCs and leukemia blasts. Its ligand, CXCL12, is expressed on marrow stromal cells, and the receptor/ligand interaction is essential for HSC homing to the marrow.2 The adverse prognostic impact of higher leukemic cell expression of CXCR44 highlights the importance of the CXCR4/CXCL12 interaction in protection of leukemic blasts by the marrow microenvironment. The CXCR4 antagonist bicyclam AMD3100 (plerixafor) blocks CXCR4/CXCL12 signaling and stromal/HSC and stromal/leukemia cell interactions, fostering dislodgement of not only HSCs, but also of leukemic cells, from their structurally and functionally defined marrow niche. Displacement of leukemic cells from the marrow by CXCR4 inhibition has been demonstrated in vitro,5 in murine models5, 6 and in patients with AML.7 Enhanced recruitment of leukemic cells from the marrow into the bloodstream appears to make them more susceptible to chemotherapy. Uy et al.7 have demonstrated the safety and feasibility of combining plerixafor with chemotherapy and shown chemosensitization in patients with relapsed or refractory AML. However, the extent of blast mobilization was modest, there was no evidence of preferential mobilization of leukemic blasts over normal cells, and although the remission rates were favorable, survival was short.

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  1. Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, USA

    E A Copelan

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Copelan, E. Leukemia cell mobilization: a road to eradication?. Bone Marrow Transplant 50, 905–906 (2015). https://doi.org/10.1038/bmt.2015.78

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