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Dendritic Cells in CML

Defective blood dendritic cells in chronic myeloid leukemia correlate with high plasmatic VEGF and are not normalized by imatinib mesylate

Abstract

Human blood dendritic cells (DC) comprise plasmacytoid DC (PDC) and myeloid DC (MDC), which both prime antitumor T-cell responses. We prospectively monitored blood DC in 30 chronic myeloid leukemia (CML) patients before and after imatinib mesylate therapy. We found a dramatic reduction in PDC and MDC prior treatment. This reduction was associated with high plasmatic vascular endothelial growth factor (VEGF), a central regulator of angiogenesis which also participates to tumor-associated immune deficiencies. Phenotypic analysis of DC revealed in some patients a deficient expression of BDCA-4/neuropilin-1 on PDC, a molecule involved in angiogenesis and DC-T-cell interactions. High VEGF correlated to an altered Th1/Th2 balance in vivo and shifted PDC-induced T-cell polarization towards Th2 in vitro. Upon imatinib treatment, plasmatic VEGF rapidly decreased and a normal BDCA-4 expression was restored. PDC and MDC increased but did not reach the levels observed in healthy individuals. We conclude that VEGF may be a key player in blood DC deficiency in CML and we show that imatinib inhibits VEGF overproduction. Incomplete recovery of blood DC under imatinib despite VEGF normalization suggests a negative impact of this drug on dendritopoiesis in vivo and may result in a sustained defect in DC-mediated anti-CML responses.

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Acknowledgements

We thank Dr Lionel Adès, Dr Jean-Marc Zini and staff members from the clinical investigation center from Saint Louis hospital for help with collecting patients samples.

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Correspondence to D Rea.

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This work was supported by a grant from La Fondation de France (2002-2386), la Délégation Régionale à la Recherche Clinique de l'Assistance Publique des Hôpitaux de Paris and Allostem (FP6 #503319).

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Boissel, N., Rousselot, P., Raffoux, E. et al. Defective blood dendritic cells in chronic myeloid leukemia correlate with high plasmatic VEGF and are not normalized by imatinib mesylate. Leukemia 18, 1656–1661 (2004). https://doi.org/10.1038/sj.leu.2403474

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