High-throughput sequencing of the T cell receptor β gene identifies aggressive early-stage mycosis fungoides.
High-throughput sequencing of the T cell receptor β gene identifies aggressive early-stage mycosis fungoides.
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DOI：
10.1126/scitranslmed.aar5894
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发表时间：
2018-05-09
影响因子：
17.1
通讯作者：
Kupper TS
中科院分区：
文献类型：
--
作者：
de Masson A;O'Malley JT;Elco CP;Garcia SS;Divito SJ;Lowry EL;Tawa M;Fisher DC;Devlin PM;Teague JE;Leboeuf NR;Kirsch IR;Robins H;Clark RA;Kupper TS
蕈样肉芽肿 (MF) 是最常见的皮肤 T 细胞淋巴瘤 (CTCL)，是一种皮肤亲性记忆 T 细胞的恶性肿瘤。大多数 MF 病例表现为早期（I A/B 期，仅限于皮肤），这些患者通常具有慢性、惰性的临床病程。然而，一小部分早期病例会发展为进行性和致命的疾病。由于结果可能如此不同，因此早期识别这一高危人群是一个紧迫的未满足的临床需求。我们评估了 T 细胞受体 β 基因 (TCRB) 的下一代高通量 DNA 测序在皮损皮肤活检中的应用，以预测来自 15 年纵向观察性临床研究的 208 名 CTCL 患者（其中 177 名患有 MF）的发现队列的进展和生存。我们将这些数据与 101 名 CTCL 患者（其中 87 名患有 MF）的独立验证队列的结果进行了比较。通过 TCRB 基因的高通量测序测量的病变皮肤中的肿瘤克隆频率 (TCF) 是 CTCL（尤其是 MF）患者无进展生存和总生存的独立预后因素。在早期患者中，皮肤 TCF>25% 的 PFS HR 高于任何其他已确定的预后因素（IB 期与 IA 期、斑块的存在、高血乳酸脱氢酶浓度、大细胞转化或年龄）。因此，TCF 是一种可以准确预测早期 MF 疾病进展的生物标志物。早期识别进展高风险的患者有助于在疾病变得难治性之前识别出可能受益于同种异体造血干细胞移植的候选人。皮肤T细胞淋巴瘤病变中的恶性T细胞克隆频率是早期疾病进展和死亡的独立生物标志物。
Mycosis fungoides (MF), the most common cutaneous T cell lymphoma (CTCL) is a malignancy of skin-tropic memory T cells. Most MF cases present as early stage (Stage I A/B, limited to skin), and these patients typically have a chronic, indolent clinical course. A small subset of early-stage cases, however, develop progressive and fatal disease. Because outcomes can be so different, early identification of this high-risk population is an urgent unmet clinical need. We evaluated the use of next-generation high-throughput DNA sequencing of the T cell receptor β gene (TCRB) in lesional skin biopsies to predict progression and survival in a discovery cohort of 208 patients with CTCL (177 with MF) from a 15-year longitudinal observational clinical study. We compared these data to the results in an independent validation cohort of 101 CTCL patients (87 with MF). The tumor clone frequency (TCF) in lesional skin, measured by high-throughput sequencing of the TCRB gene, was an independent prognostic factor of both progression-free and overall survival in patients with CTCL, and MF in particular. In early-stage patients, a TCF>25% in skin had a higher HR for PFS than any other established prognostic factor (stage IB versus IA, presence of plaques, high blood lactate dehydrogenase concentration, large-cell transformation, or age). The TCF is therefore a biomarker that accurately predicts disease progression in early-stage MF. Early identification of patients at high risk for progression could help identify candidates who may benefit from allogeneic hematopoietic stem cell transplantation before their disease becomes treatment-refractory. The malignant T cell clone frequency in cutaneous T cell lymphoma lesions is an independent biomarker for early disease progression and death.
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影响因子：
30.8
作者：
da Silva Almeida AC;Abate F;Khiabanian H;Martinez-Escala E;Guitart J;Tensen CP;Vermeer MH;Rabadan R;Ferrando A;Palomero T
通讯作者：
Palomero T
影响因子：
20.3
作者：
Jackow, CM;Cather, JC;Duvic, M
通讯作者：
Duvic, M
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
11.5
作者：
Litvinov, Ivan V.;Jones, David A.;Kupper, Thomas S.
通讯作者：
Kupper, Thomas S.
影响因子：
6.5
作者：
Ponti, Renata;Fierro, Maria T.;Bernengo, Maria G.
通讯作者：
Bernengo, Maria G.