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No role for CXCL12–G801A polymorphism in the development of extramedullary disease in acute myeloid leukemia

Leukemia volume 22, pages 669–671 (2008)Cite this article

CXCL12, or stromal cell-derived factor-1 (SDF-1), initially identified as a pre-B-cell growth-stimulating factor, is constitutively synthesized and released by bone marrow (BM) stromal cells. CXCL12 signals through CXCR4, a seven transmembrane, G-protein-coupled receptor, which is broadly expressed on a variety of normal cells, either belonging or not belonging to the hematopoietic system.1 There is an extensive body of data concerning the prominent function of CXCL12 as a potent chemoattractant for various hematopoietic cells, including the CD34+ hematopoietic progenitor cell (HPC); indeed, the CXCL12–CXCR4 axis is considered as the major player in the regulation of homing and retention of HPC in the marrow microenvironment.1 In addition, CXCL12 interaction with CXCR4 expressed on tumor cells may favor their survival and growth in a paracrine manner, beyond promoting their metastatic spread in organs where the level of CXCL12 reaches a critical threshold.2

Acute myeloid leukemia (AML) cells express functional CXCR4 and respond to CXCL12 in a complex way that involves not only chemotaxis and migration beneath marrow stromal cells and to the peripheral blood (PB), but also the regulation of cell cycle progression.3 In a prospective study in AML patients, low expression of CXCR4 on the membrane of blast cells by flow cytometry associated with a longer relapse-free and overall survival, and CXCR4 expression level maintained an independent prognostic value together with unfavorable cytogenetics in a multivariate analysis.4 The role of CXCR4 in circulation of leukemic blasts and the development of extramedullary disease has been explored also in childhood acute lymphoblastic leukemia. A significant correlation between high-membrane level of CXCR4 and the enlargement of spleen or liver was found, independently of the count of lymphoblasts in the circulation.5 Finally, elevated level of submicron plasma membrane vesicles expressing CXCR4 has been detected in the blood and BM fluids of AML patients, providing further evidence that the CXCR4–CXCL12 axis intervenes in AML cell trafficking and tissue dissemination.6

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Acknowledgements

This work was supported by a grant from Fondazione Ente Cassa di Risparmio di Firenze and Instituto Toscano Tumori.

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  1. Department of Hematology, University of Florence, Florence, Italy

    V Ponziani, F Mannelli, N Bartalucci, G Gianfaldoni, F Leoni, E Antonioli, P Guglielmelli, S Ciolli, A Bosi & A M Vannucchi

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  1. V Ponziani
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Correspondence to A M Vannucchi.

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Ponziani, V., Mannelli, F., Bartalucci, N. et al. No role for CXCL12–G801A polymorphism in the development of extramedullary disease in acute myeloid leukemia. Leukemia 22, 669–671 (2008). https://doi.org/10.1038/sj.leu.2404938

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