High-throughput sequencing of the T cell receptor β gene identifies aggressive early-stage mycosis fungoides.
Adele de MassonJohn T O'MalleyChristopher P ElcoSarah S GarciaSherrie J DivitoElizabeth L LowryMarianne TawaDavid C FisherPhillip M DevlinJessica E TeagueNicole R LeboeufIlan R KirschHarlan S RobinsRachael A ClarkThomas S KupperPublished in: Science translational medicine (2019)
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.
Keyphrases
- early stage
- prognostic factors
- end stage renal disease
- ejection fraction
- high throughput
- allogeneic hematopoietic stem cell transplantation
- newly diagnosed
- chronic kidney disease
- single cell
- high throughput sequencing
- genome wide
- copy number
- small molecule
- wound healing
- soft tissue
- peritoneal dialysis
- acute lymphoblastic leukemia
- gene expression
- squamous cell carcinoma
- bone marrow
- metabolic syndrome
- working memory
- stem cells
- multiple sclerosis
- dna methylation
- machine learning
- artificial intelligence
- insulin resistance
- lymph node
- cell free
- cross sectional
- smoking cessation
- free survival
- big data
- drug induced
- cell therapy