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High-throughput sequencing of the T cell receptor β gene identifies aggressive early-stage mycosis fungoides.

Abstract：

: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 the skin), and these patients typically have a chronic, indolent clinical course. However, a small subset of early-stage cases 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 of >25% in the skin was a stronger predictor of progression 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 therefore may accurately predict 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.

journal_name

Sci Transl Med

journal_title

Science translational medicine

authors

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

doi

10.1126/scitranslmed.aar5894

subject

Has Abstract

pub_date

2018-05-09 00:00:00

issue

440

eissn

1946-6234

issn

1946-6242

pii

10/440/eaar5894

journal_volume

10

pub_type

杂志文章

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