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Tumor supernatant from myeloid malignancies inhibits T-cell apoptosis and cell cycle entry independently

Leukemia volume 19, pages 1699–1702 (2005)Cite this article

TO THE EDITOR

A number of malignancies such as melanoma, ovarian cancer, renal cell carcinoma and glioma produce an immunosuppressive microenvironment.1 We have shown that acute myeloid leukemia (AML) tumor-derived supernatant (TSN) is immunosuppressive, preventing T-cell activation, proliferation and apoptosis.2 AML TSN prevents T-cell activation by profoundly inhibiting the production of the Th1 cytokines IFN-γ and IL-2 and inhibits cell cycle entry before the G0 → G1 commitment point,3 by preventing the phosphorylation of retinoblastoma protein (pRb) and the induction of c-Myc.1 In addition, AML TSN delays the apoptosis of both normal hematopoietic and leukemic blast cells;2 however, it was unknown as to whether this is a unique feature of AML or extended to other myeloid malignancies. We now show that T-cell apoptosis is inhibited by TSN from the cells of 11/12 cases of chronic myeloid leukemia (CML) and myelodysplastic syndrome (MDS) tested, irrespective of disease severity. We suggest that myeloid malignancies generate an antiapoptotic microenvironment, which favors the survival of malignant cells. Apoptosis of normal T cells is inhibited and the AML TSN renders these T cells functionally incompetent. In contrast, IL-2 production and phosphorylation of the pRb is inhibited by the majority of high-grade and some low-grade disease cases, whereas c-Myc induction is inhibited only by AML TSN. This strongly suggests the presence of multiple factors in TSN that target apoptotic and cell cycle processes individually.

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Authors and Affiliations

  1. Department of Haematological and Molecular Medicine, King's College London, Rayne Institute, London, UK

    D Milojkovic, A G S Buggins, S Devereux, N S B Thomas & G J Mufti

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  1. D Milojkovic
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  2. A G S Buggins
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  3. S Devereux
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  4. N S B Thomas
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  5. G J Mufti
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Correspondence to D Milojkovic.

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Milojkovic, D., Buggins, A., Devereux, S. et al. Tumor supernatant from myeloid malignancies inhibits T-cell apoptosis and cell cycle entry independently. Leukemia 19, 1699–1702 (2005). https://doi.org/10.1038/sj.leu.2403864

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