Clinical significance of TP53 mutations in adult T-cell leukemia/lymphoma.
Clinical significance of TP53 mutations in adult T-cell leukemia/lymphoma.
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成人T细胞白血病/淋巴瘤中TP 53突变的临床意义
DOI：
10.1111/bjh.17749
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发表时间：
2021-11
影响因子：
6.5
通讯作者：
Inagaki, Hiroshi
中科院分区：
文献类型：
--
作者：
Sakamoto, Yuma;Ishida, Takashi;Masaki, Ayako;Murase, Takayuki;Takeshita, Morishige;Muto, Reiji;Iwasaki, Hiromi;Ito, Asahi;Kusumoto, Shigeru;Nakano, Nobuaki;Tokunaga, Masahito;Yonekura, Kentaro;Tashiro, Yukie;Iida, Shinsuke;Utsunomiya, Atae;Ueda, Ryuzo;Inagaki, Hiroshi
成人 T 细胞白血病/淋巴瘤 (ATL) 患者预后较差。在这里，我们研究了 TP53 基因突变对不同方式治疗的 ATL 预后的影响。在 177 名患者中，我们在 37 名患者中鉴定出了 47 个 TP53 基因的单核苷酸变异或插入缺失 (SNV/indel)。在 38 名患者中观察到 TP53 拷贝数变异 (CNV)。总共，177 名患者中有 67 名携带 TP53 SNV/插入缺失或 TP53 CNV，并被归类为具有 TP53 突变。在整个队列中，有和没有TP53突变的患者的中位生存期分别为1·0和6·7年（P < 0·001）。异基因造血干细胞移植（HSCT）后，TP53突变患者（n = 16）和无TP53突变患者（n = 29）的中位生存期分别为0·4年，未达到（P = 0·001）。对于接受mogamulizumab但未进行同种异体HSCT的患者，TP53突变患者（n = 27）从第一剂抗体起的中位生存期仅为0·9年，而无TP53突变的患者（n = 42；P < 0·001）为5·1年。因此，无论治疗策略如何，TP53 突变都与 ATL 的不良预后相关。需要建立替代方法来克服 TP53 突变对 ATL 患者的不利影响。
Adult T‐cell leukaemia/lymphoma (ATL) patients have a poor prognosis. Here, we investigated the impact of TP53 gene mutations on prognosis of ATL treated in different ways. Among 177 patients, we identified 47 single nucleotide variants or insertion‐deletions (SNVs/indels) of the TP53 gene in 37 individuals. TP53 copy number variations (CNVs) were observed in 38 patients. Altogether, 67 of 177 patients harboured TP53 SNVs/indels or TP53 CNVs, and were categorized as having TP53 mutations. In the entire cohort, median survival of patients with and without TP53 mutations was 1·0 and 6·7 years respectively (P < 0·001). After allogeneic haematopoietic stem cell transplantation (HSCT), median survival of patients with (n = 16) and without (n = 29) TP53 mutations was 0·4 years and not reached respectively (P = 0·001). For patients receiving mogamulizumab without allogeneic HSCT, the median survival from the first dose of antibody in patients with TP53 mutations (n = 27) was only 0·9 years, but 5·1 years in those without (n = 42; P < 0·001). Thus, TP53 mutations are associated with unfavourable prognosis of ATL, regardless of treatment strategy. The establishment of alternative modalities to overcome the adverse impact of TP53 mutations in patients with ATL is required.
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影响因子：
3.7
作者：
Romeo M;Hutchison T;Malu A;White A;Kim J;Gardner R;Smith K;Nelson K;Bergeson R;McKee R;Harrod C;Ratner L;Lüscher B;Martinez E;Harrod R
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Harrod R
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168.9
作者：
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通讯作者：
Zinzan, Pier Luigi
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5.7
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Ishida T;Utsunomiya A;Jo T;Yamamoto K;Kato K;Yoshida S;Takemoto S;Suzushima H;Kobayashi Y;Imaizumi Y;Yoshimura K;Kawamura K;Takahashi T;Tobinai K;Ueda R
通讯作者：
Ueda R
影响因子：
4.7
作者：
Ohsugi, Takeo;Ishida, Takaomi;Umezawa, Kazuo
通讯作者：
Umezawa, Kazuo
影响因子：
9.7
作者：
Tawara, M;Hogerzeil, SJ;Kamihira, S
通讯作者：
Kamihira, S