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Cells of adult T-cell leukemia evade HTLV-1 Tax/NF-κB hyperactivation–induced senescence
| العنوان: | Cells of adult T-cell leukemia evade HTLV-1 Tax/NF-κB hyperactivation–induced senescence |
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| المؤلفون: | Shudofsky, Abigail M. Druck, Giam, Chou-Zen |
| المصدر: | Blood Advances; February 2019, Vol. 3 Issue: 4 p564-569, 6p |
| مستخلص: | Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATL). The HTLV-1 viral trans-activator/oncoprotein Tax is a major driver of ATL, yet it induces rapid p21Cip1/Waf1 (p21)- and p27Kip1-mediated cellular senescence through constitutive activation (hyperactivation) of NF-κB. Although constitutive NF-κB activation is a common feature of T/B-cell leukemia/lymphoma, including ATL, it is not known how ATL cells maintain chronic NF-κB activation without undergoing senescence. Here, we demonstrate that, in contrast to HTLV-1− T-cell lines, ATL cell lines no longer undergo Tax-induced senescence. Although Tax+ and Tax− ATL cell lines showed signatures of constitutive NF-κB activation, their ability to progress through the cell cycle was unaffected. In some cases, ATL cell lines continued to proliferate despite significant upregulation of p21; additionally, many cell lines displayed altered expression of G1 and G1/S cyclins, particularly overexpression of cyclin D2. We propose that, during the course of ATL development, leukemia cells acquire genetic/epigenetic changes that can mitigate the senescence response triggered by NF-κB hyperactivation. Restoring the NF-κB–induced senescence response would likely help to control the development and progression of ATL and similar lymphoid malignancies. |
| قاعدة البيانات: | Supplemental Index |
Full Text Finder | تدمد: | 24739529 24739537 |
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| DOI: | 10.1182/bloodadvances.2018029322 |