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Sézary syndrome originates from heavily mutated hematopoietic progenitors.

Publication ,  Journal Article
Harro, CM; Sprenger, KB; Chaurio, RA; Powers, JJ; Innamarato, P; Anadon, CM; Zhang, Y; Biswas, S; Mandal, G; Mine, JA; Cortina, C; Nagy, MZ ...
Published in: Blood Adv
September 26, 2023

The pathogenesis of cutaneous T-cell lymphoma (CTCL) remains unclear. Using single-cell RNA or T-cell receptor (TCR) sequencing of 32 619 CD3+CD4+ and CD26+/CD7+ and 29 932 CD3+CD4+ and CD26-/CD7- lymphocytes from the peripheral blood of 7 patients with CTCL, coupled to single-cell ATAC-sequencing of 26,411 CD3+CD4+ and CD26+/CD7+ and 33 841 CD3+CD4+ and CD26-/CD7- lymphocytes, we show that tumor cells in Sézary syndrome 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 patients with Sézary syndrome. 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.

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Published In

Blood Adv

DOI

EISSN

2473-9537

Publication Date

September 26, 2023

Volume

7

Issue

18

Start / End Page

5586 / 5602

Location

United States

Related Subject Headings

  • Skin Neoplasms
  • Sezary Syndrome
  • Receptors, Antigen, T-Cell
  • Mycosis Fungoides
  • Lymphoma, T-Cell, Cutaneous
  • Humans
  • Dipeptidyl Peptidase 4
  • 3201 Cardiovascular medicine and haematology
 

Citation

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Harro, C. M., Sprenger, K. B., Chaurio, R. A., Powers, J. J., Innamarato, P., Anadon, C. M., … Conejo-Garcia, J. R. (2023). Sézary syndrome originates from heavily mutated hematopoietic progenitors. Blood Adv, 7(18), 5586–5602. https://doi.org/10.1182/bloodadvances.2022008562
Harro, Carly M., Kimberly B. Sprenger, Ricardo A. Chaurio, John J. Powers, Patrick Innamarato, Carmen M. Anadon, Yumeng Zhang, et al. “Sézary syndrome originates from heavily mutated hematopoietic progenitors.Blood Adv 7, no. 18 (September 26, 2023): 5586–5602. https://doi.org/10.1182/bloodadvances.2022008562.
Harro CM, Sprenger KB, Chaurio RA, Powers JJ, Innamarato P, Anadon CM, et al. Sézary syndrome originates from heavily mutated hematopoietic progenitors. Blood Adv. 2023 Sep 26;7(18):5586–602.
Harro, Carly M., et al. “Sézary syndrome originates from heavily mutated hematopoietic progenitors.Blood Adv, vol. 7, no. 18, Sept. 2023, pp. 5586–602. Pubmed, doi:10.1182/bloodadvances.2022008562.
Harro CM, Sprenger KB, Chaurio RA, Powers JJ, Innamarato P, Anadon CM, Zhang Y, Biswas S, Mandal G, Mine JA, Cortina C, Nagy MZ, Martin AL, Handley KF, Borjas GJ, Chen P-L, Pinilla-Ibarz J, Sokol L, Yu X, Conejo-Garcia JR. Sézary syndrome originates from heavily mutated hematopoietic progenitors. Blood Adv. 2023 Sep 26;7(18):5586–5602.

Published In

Blood Adv

DOI

EISSN

2473-9537

Publication Date

September 26, 2023

Volume

7

Issue

18

Start / End Page

5586 / 5602

Location

United States

Related Subject Headings

  • Skin Neoplasms
  • Sezary Syndrome
  • Receptors, Antigen, T-Cell
  • Mycosis Fungoides
  • Lymphoma, T-Cell, Cutaneous
  • Humans
  • Dipeptidyl Peptidase 4
  • 3201 Cardiovascular medicine and haematology