PMID- 34583709
OWN - NLM
STAT- MEDLINE
DCOM- 20220224
LR  - 20220224
IS  - 1476-4598 (Electronic)
IS  - 1476-4598 (Linking)
VI  - 20
IP  - 1
DP  - 2021 Sep 28
TI  - Single-cell RNA sequencing reveals markers of disease progression in primary 
      cutaneous T-cell lymphoma.
PG  - 124
LID - 10.1186/s12943-021-01419-2 [doi]
LID - 124
AB  - BACKGROUND: In early-stage mycosis fungoides (MF), the most common primary 
      cutaneous T-cell lymphoma, limited skin involvement with patches and plaques is 
      associated with a favorable prognosis. Nevertheless, approximately 20-30% of 
      cases progress to tumors or erythroderma, resulting in poor outcome. At present, 
      factors contributing to this switch from indolent to aggressive disease are only 
      insufficiently understood. METHODS: In patients with advanced-stage MF, we 
      compared patches with longstanding history to newly developed plaques and tumors 
      by using single-cell RNA sequencing, and compared results with early-stage MF as 
      well as nonlesional MF and healthy control skin. RESULTS: Despite considerable 
      inter-individual variability, lesion progression was uniformly associated with 
      downregulation of the tissue residency markers CXCR4 and CD69, the heat shock 
      protein HSPA1A, the tumor suppressors and immunoregulatory mediators ZFP36 and 
      TXNIP, and the interleukin 7 receptor (IL7R) within the malignant clone, but not 
      in benign T cells. This phenomenon was not only found in conventional TCR-alphabeta MF, 
      but also in a case of TCR-gammadelta MF, suggesting a common mechanism across MF 
      subtypes. Conversely, malignant cells in clinically unaffected skin from MF 
      patients showed upregulation of these markers. CONCLUSIONS: Our data reveal a 
      specific panel of biomarkers that might be used for monitoring MF disease 
      progression. Altered expression of these genes may underlie the switch in 
      clinical phenotype observed in advanced-stage MF.
CI  - (c) 2021. The Author(s).
FAU - Rindler, Katharina
AU  - Rindler K
AD  - Department of Dermatology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria.
FAU - Jonak, Constanze
AU  - Jonak C
AD  - Department of Dermatology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria.
FAU - Alkon, Natalia
AU  - Alkon N
AD  - Department of Dermatology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria.
FAU - Thaler, Felix M
AU  - Thaler FM
AD  - Department of Dermatology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria.
FAU - Kurz, Harald
AU  - Kurz H
AD  - Department of Dermatology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria.
FAU - Shaw, Lisa E
AU  - Shaw LE
AD  - Department of Dermatology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria.
FAU - Stingl, Georg
AU  - Stingl G
AD  - Department of Dermatology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria.
FAU - Weninger, Wolfgang
AU  - Weninger W
AD  - Department of Dermatology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria.
FAU - Halbritter, Florian
AU  - Halbritter F
AD  - St. Anna Children's Cancer Research Institute (CCRI), Zimmermannplatz 10, 1090, 
      Vienna, Austria.
FAU - Bauer, Wolfgang M
AU  - Bauer WM
AD  - Department of Dermatology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria.
FAU - Farlik, Matthias
AU  - Farlik M
AD  - Department of Dermatology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria.
FAU - Brunner, Patrick M
AU  - Brunner PM
AUID- ORCID: 0000-0002-3488-3345
AD  - Department of Dermatology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria. patrick.brunner@meduniwien.ac.at.
LA  - eng
GR  - KLI 849-B/Austrian Science Fund/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210928
PL  - England
TA  - Mol Cancer
JT  - Molecular cancer
JID - 101147698
RN  - 0 (Biomarkers)
SB  - IM
MH  - Adult
MH  - Aged
MH  - *Biomarkers
MH  - Biopsy
MH  - Computational Biology/methods
MH  - Disease Progression
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - Lymphoma, T-Cell, Cutaneous/*genetics/*pathology
MH  - Male
MH  - Middle Aged
MH  - Mycosis Fungoides/genetics/pathology
MH  - Phenotype
MH  - *RNA-Seq
MH  - Sequence Analysis, RNA
MH  - *Single-Cell Analysis/methods
PMC - PMC8477535
OTO - NOTNLM
OT  - Advanced-stage MF
OT  - Cutaneous lymphoma
OT  - Early-stage MF
OT  - Gamma-delta lymphoma
OT  - Mycosis fungoides
OT  - Nonlesional MF
OT  - Single-cell RNA sequencing
COIS- CJ is an employee of the Medical University of Vienna, and has received personal 
      fees from LEO Pharma, Pfizer, Recordati Rare Diseases, Eli Lilly and Company, 
      Novartis, Takeda, Mallinckrodt/Therakos, AbbVie, Janssen, Sandoz, Kyowa Kirin and 
      Almirall independently from this work. CJ is an investigator for Eli Lilly and 
      Company, LEO Pharma, Novartis, and 4SC (grant paid to her institution). GS 
      received personal fees from Boehringer Ingelheim, Sanofi-Genzyme, Almirall, and 
      Novartis. WW is an employee of the Medical University of Vienna and has received 
      personal fees from LEO Pharma, Pfizer, Sanofi Genzyme, Eli Lilly, Novartis, 
      Boehringer Ingelheim, AbbVie, and Janssen. WMB is an employee of the Medical 
      University of Vienna and has received personal fees from Takeda, Abbvie, GSK/ViiV 
      and Gilead. PMB is an employee of the Medical University of Vienna, and has 
      received personal fees from LEO Pharma, Pfizer, Sanofi Genzyme, Eli Lilly, 
      Novartis, Celgene, UCB Pharma, Biotest, Boehringer Ingelheim, AbbVie, Amgen, 
      Arena Pharmaceuticals, GSK and Regeneron independently from this work. PMB is an 
      investigator for Novartis (grant paid to his institution). The rest of the 
      authors declare that they have no relevant conflicts of interest.
EDAT- 2021/09/30 06:00
MHDA- 2022/02/25 06:00
PMCR- 2021/09/28
CRDT- 2021/09/29 05:39
PHST- 2021/05/26 00:00 [received]
PHST- 2021/08/28 00:00 [accepted]
PHST- 2021/09/29 05:39 [entrez]
PHST- 2021/09/30 06:00 [pubmed]
PHST- 2022/02/25 06:00 [medline]
PHST- 2021/09/28 00:00 [pmc-release]
AID - 10.1186/s12943-021-01419-2 [pii]
AID - 1419 [pii]
AID - 10.1186/s12943-021-01419-2 [doi]
PST - epublish
SO  - Mol Cancer. 2021 Sep 28;20(1):124. doi: 10.1186/s12943-021-01419-2.