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Acute Lymphoblastic Leukemia

Dichotomy of all-trans retinoic acid inducing signals for adult T-cell leukemia

Leukemia volume 19, pages 1010–1017 (2005)Cite this article

Abstract

We previously reported that all-trans retinoic acid (ATRA) inhibits growth in human T-cell leukemia virus type 1 (HTLV-1)-positive T-cell lines and fresh cells from patients with adult T-cell leukemia. However, the mechanism of this inhibition is not clear. In the present study, we observed that NF-κB transcriptional activity as well as cell growth decreased significantly in HTLV-1-positive T-cell lines in the presence of ATRA. Furthermore, we observed that ATRA reduced HTLV-1 proviral DNA, HTLV-1 genes (gag, tax, or pol mRNA) using the real-time quantitative polymerase chain reaction. SIL-2R was reduced by ATRA in both protein level (culture supernantant) and mRNA level in HTLV-1-positive T-cell lines. Interestingly, ATRA significantly inhibited RT activity similar to azidothimidine (AZT) in HTLV-1-positive T-cell lines. Moreover, AZT inhibited proviral DNA but not NF-κB transcriptional activity, and sIL-2R on HTLV-1; however, ATRA inhibited of NF-κB, proviral DNA and sIL-2R on HTLV-1. These results suggested that the decrease in sIL-2R induced by ATRA may be caused by the actions of a NF-κB inhibitor acting on the NF-κB/sIL-2R signal pathway. These results suggested that ATRA could have two roles, as a NF-κB inhibitor and as an RT inhibitor.

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  1. Department of Hematology, Kinki University School of Medicine, Osaka, Japan

    T Yamaguchi, Y Maeda, S Ueda, Y Hijikata, Y Morita, J-i Miyatake, M Matsuda & A Kanamaru

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Correspondence to Y Maeda.

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Yamaguchi, T., Maeda, Y., Ueda, S. et al. Dichotomy of all-trans retinoic acid inducing signals for adult T-cell leukemia. Leukemia 19, 1010–1017 (2005). https://doi.org/10.1038/sj.leu.2403760

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