Sézary syndrome originates from heavily mutated hematopoietic progenitors.
Carly M HarroKimberly B SprengerRicardo A ChaurioJoseph PidalaPatrick InnamaratoCarmen M AnadonYumeng ZhangSubir BiswasGunjan MandalJessica A MineCarla CortinaMate Z NagyAlexandra L MartinKatelyn F HandleyGustavo J BorjasPei-Ling ChenJavier Pinilla-IbarzLubomir SokolXiaoqing YuJose R Conejo-GarciaPublished in: Blood advances (2023)
The pathogenesis of Cutaneous T cell lymphoma (CTCL) remains unclear. Using single-cell RNA/TCR sequencing of 32,619 CD3+CD4+, CD26+/CD7+ and 29,932 CD3+CD4+, CD26-/CD7- lymphocytes from the peripheral blood of 7 patients with CTCL, coupled to single-cell ATAC-seq of 26,411 CD3+CD4+, CD26+/CD7+ and 33,841 CD3+CD4+, CD26-/CD7- lymphocytes, we show that tumor cells in Sézary syndrome (SS) and Mycosis fungoides (MF) exhibit different phenotypes and trajectories of differentiation. When compared to MF, Sézary cells exhibit narrower repertoires of TCRs and exhibit clonal enrichment. Surprisingly, we identified ≥200 mutations in hematopoietic stem cells from multiple Sézary syndrome patients. Mutations in key oncogenes were also present in peripheral Sézary cells, which also showed the hallmarks of recent thymic egression. Together our data suggest that CTCL arises from mutated lymphocyte progenitors that acquire TCRs in the thymus, which complete their malignant transformation in the periphery.
Keyphrases
- single cell
- peripheral blood
- rna seq
- induced apoptosis
- cell cycle arrest
- end stage renal disease
- case report
- high throughput
- newly diagnosed
- ejection fraction
- chronic kidney disease
- bone marrow
- prognostic factors
- gene expression
- signaling pathway
- oxidative stress
- peritoneal dialysis
- regulatory t cells
- electronic health record
- genome wide
- cell proliferation
- pi k akt
- wild type