Reinstated p53 response and high anti-T-cell leukemia activity by the novel alkylating deacetylase inhibitor tinostamustine
Reinstated p53 response and high anti-T-cell leukemia activity by the novel alkylating deacetylase inhibitor tinostamustine
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DOI：
10.1038/s41375-020-0772-6
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发表时间：
2020-02
期刊：
影响因子：
11.4
通讯作者：
S. Pützer;L. Varghese;J. von Jan;T. Braun;A. Giri;P. Mayer;N. Riet;S. Timonen;S. Oberbeck;H. Kuusanmäki;S. Mustjoki;M. Stern;T. Aittokallio;S. Newrzela;A. Schrader;M. Herling
中科院分区：
文献类型：
--
作者：
S. Pützer;L. Varghese;J. von Jan;T. Braun;A. Giri;P. Mayer;N. Riet;S. Timonen;S. Oberbeck;H. Kuusanmäki;S. Mustjoki;M. Stern;T. Aittokallio;S. Newrzela;A. Schrader;M. Herling
T细胞幼淋巴细胞白血病（T-PLL）是西方国家最常见的成熟T细胞白血病。其固有的侵袭性生长和众所周知的化疗难治性行为导致总生存时间< 20-36个月[1，2]。T-PLL尚无正式许可的药物，尽管抗CD 52单克隆抗体Alemtuzumab诱导了较高的初次缓解率，但绝大多数患者平均在此后12个月内复发[3，4]。中位年龄为63岁，诱导后条件使50-70%的患者不适合异基因干细胞移植。此外，只有20-30%的移植患者可以实现长期疾病控制。总体而言，T-PLL仍然是一种未充分解决的罕见实体，迫切需要新的治疗设计。
T-cell prolymphocytic leukemia (T-PLL) is the most frequent mature T-cell leukemia in Western countries. Its inherently aggressive growth and a notoriously chemotherapy refractory behavior result in overall survival times of< 20–36 months [1, 2]. There are no formally licensed drugs for T-PLL.Although the anti-CD52 monoclonal antibody alemtuzumab induces high primary response rates, the vast majority of patients relapse on average within 12 months thereafter [3, 4]. Presentation at a median age of 63 years and post-induction conditions render 50–70% of patients ineligible for allogeneic stem cell transplantation. Moreover, long-term disease control can only be accomplished for a proportion of 20–30% of transplanted patients. Overall, T-PLL remains an insufficiently addressed rare entity with urgently needed novel treatment designs.