New Genetic Markers of Skin T-Cell Lymphoma Treatment

J 2024

New Genetic Markers of Skin T-Cell Lymphoma Treatment

VAŠKŮ, Vladimír, Petra FIALOVÁ and Anna VAŠKŮ

Basic information

Original name

New Genetic Markers of Skin T-Cell Lymphoma Treatment

Authors

VAŠKŮ, Vladimír (203 Czech Republic, belonging to the institution), Petra FIALOVÁ (203 Czech Republic, belonging to the institution) and Anna VAŠKŮ (203 Czech Republic, belonging to the institution)

Edition

GENES, BASEL, MDPI, 2024, 2073-4425

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30216 Dermatology and venereal diseases

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.500 in 2022

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.3390/genes15030358

UT WoS

001193031400001

Keywords in English

CTCL; CD147; HLA DRB1*1501

Abstract

V originále

Aim: Cutaneous T-cell lymphomas (CTCL) can be described as chronic skin inflammation lesions with the content of malignant T cells and they are considered to be T-cell-mediated skin diseases. CD147 is recognized as a 58-kDa cell surface glycoprotein of the immunoglobulin superfamily; it can induce the synthesis of MMPs (matrix metalloproteinases) on the surface of tumor cells where it was originally identified. It can also function in adjacent tumor fibroblasts using CD147-CD147 interactions. The polymorphism rs8259 T/A is situated in the untranslated region (3 ' UTR) of the CD147 gene. HLA DRB1*1501 takes part in the process of presentation and recognition of different antigens to T cells. It can be expressed by antigen-presenting cells-macrophages, dendritic cells, and B cells. The aim of the study is to test genotype-phenotype associations of both polymorphisms including therapy in a large cohort of CTCL patients. Materials and Methods: A final total of 104 CTCL patients were enrolled in the study. For the first remission at the clinic department, they were treated by means of local skin-directed therapy, phototherapy, and systemic therapy. Genomic DNA was isolated from peripheral blood leukocytes. A standard technique using proteinase K was applied. The polymorphisms rs8259 T/A (CD147 gene) and rs3135388 (HLA DRB1*1501) were detected through standard PCR-restriction fragment length polymorphism methods. Results: The severity of the disease (patients with parapsoriasis, stages IA and IB, vs patients with stages IIB, IIIA, and IIIB) was associated with the CD147 genotype: the AA variant was 3.38 times more frequent in more severe cases, which reflects the decision on systemic therapy (p = 0.02, specificity 0.965). The AA genotype in the CD147 polymorphism was 12 times more frequent in patients who underwent systemic therapy of CTCL compared to those not treated with this therapy (p = 0.009, specificity 0.976). The same genotype was also associated with radiotherapy-it was observed 14 times more frequently in patients treated with radiotherapy (p = 0.009, specificity 0.959). In patients treated with interferon alpha therapy, the AA genotype was observed to be 5.85 times more frequent compared to the patients not treated with interferon therapy (p = 0.03, specificity 0.963). The HLA DRB1*1501 polymorphism was associated with local skin-directed therapy of CTCL. The CC genotype of the polymorphism was observed to be 3.57 times more frequent in patients treated with local therapy (p = 0.008, specificity 0.948). When both polymorphisms had been calculated together, even better results were obtained: the AACC double genotype was 11 times more frequent in patients with severe CTCL (p = 0.009, specificity 0.977). The TACT double genotype was associated with local skin-directed therapy (0.09 times lower frequency, p = 0.007, sensitivity 0.982). The AACC genotype was 8.9 times more frequent in patients treated by means of systemic therapy (p = 0.02, specificity 0.976) and as many as 18.8 times more frequent in patients treated with radiotherapy (p = 0.005, specificity 0.969). Thus, the AACC double genotype of CD147 and DRB1*1501 polymorphisms seems to be a clinically highly specific marker of severity, systemic therapy and radiotherapy of patients with T-cell lymphoma. Conclusion: Although genotyping results were not known during the treatment decision and could not modify it, the clinical decision on severity and therapy reflected some aspects of the genetic background of this complicated T-cell-associated disease very well.

Citovat

VAŠKŮ, Vladimír, Petra FIALOVÁ and Anna VAŠKŮ. New Genetic Markers of Skin T-Cell Lymphoma Treatment. GENES. BASEL: MDPI, 2024, vol. 15, No 3, p. 1-9. ISSN 2073-4425. Available from: https://dx.doi.org/10.3390/genes15030358.

@article{2398777,
   author = {Vašků, Vladimír and Fialová, Petra and Vašků, Anna},
   article_location = {BASEL},
   article_number = {3},
   doi = {http://dx.doi.org/10.3390/genes15030358},
   keywords = {CTCL; CD147; HLA DRB1*1501},
   language = {eng},
   issn = {2073-4425},
   journal = {GENES},
   title = {New Genetic Markers of Skin T-Cell Lymphoma Treatment},
   url = {https://www.mdpi.com/2073-4425/15/3/358},
   volume = {15},
   year = {2024}
}

TY  - JOUR
ID  - 2398777
AU  - Vašků, Vladimír - Fialová, Petra - Vašků, Anna
PY  - 2024
TI  - New Genetic Markers of Skin T-Cell Lymphoma Treatment
JF  - GENES
VL  - 15
IS  - 3
SP  - 1-9
EP  - 1-9
PB  - MDPI
SN  - 20734425
KW  - CTCL
KW  - CD147
KW  - HLA DRB1*1501
UR  - https://www.mdpi.com/2073-4425/15/3/358
N2  - Aim: Cutaneous T-cell lymphomas (CTCL) can be described as chronic skin inflammation lesions with the content of malignant T cells and they are considered to be T-cell-mediated skin diseases. CD147 is recognized as a 58-kDa cell surface glycoprotein of the immunoglobulin superfamily; it can induce the synthesis of MMPs (matrix metalloproteinases) on the surface of tumor cells where it was originally identified. It can also function in adjacent tumor fibroblasts using CD147-CD147 interactions. The polymorphism rs8259 T/A is situated in the untranslated region (3 ' UTR) of the CD147 gene. HLA DRB1*1501 takes part in the process of presentation and recognition of different antigens to T cells. It can be expressed by antigen-presenting cells-macrophages, dendritic cells, and B cells. The aim of the study is to test genotype-phenotype associations of both polymorphisms including therapy in a large cohort of CTCL patients. Materials and Methods: A final total of 104 CTCL patients were enrolled in the study. For the first remission at the clinic department, they were treated by means of local skin-directed therapy, phototherapy, and systemic therapy. Genomic DNA was isolated from peripheral blood leukocytes. A standard technique using proteinase K was applied. The polymorphisms rs8259 T/A (CD147 gene) and rs3135388 (HLA DRB1*1501) were detected through standard PCR-restriction fragment length polymorphism methods. Results: The severity of the disease (patients with parapsoriasis, stages IA and IB, vs patients with stages IIB, IIIA, and IIIB) was associated with the CD147 genotype: the AA variant was 3.38 times more frequent in more severe cases, which reflects the decision on systemic therapy (p = 0.02, specificity 0.965). The AA genotype in the CD147 polymorphism was 12 times more frequent in patients who underwent systemic therapy of CTCL compared to those not treated with this therapy (p = 0.009, specificity 0.976). The same genotype was also associated with radiotherapy-it was observed 14 times more frequently in patients treated with radiotherapy (p = 0.009, specificity 0.959). In patients treated with interferon alpha therapy, the AA genotype was observed to be 5.85 times more frequent compared to the patients not treated with interferon therapy (p = 0.03, specificity 0.963). The HLA DRB1*1501 polymorphism was associated with local skin-directed therapy of CTCL. The CC genotype of the polymorphism was observed to be 3.57 times more frequent in patients treated with local therapy (p = 0.008, specificity 0.948). When both polymorphisms had been calculated together, even better results were obtained: the AACC double genotype was 11 times more frequent in patients with severe CTCL (p = 0.009, specificity 0.977). The TACT double genotype was associated with local skin-directed therapy (0.09 times lower frequency, p = 0.007, sensitivity 0.982). The AACC genotype was 8.9 times more frequent in patients treated by means of systemic therapy (p = 0.02, specificity 0.976) and as many as 18.8 times more frequent in patients treated with radiotherapy (p = 0.005, specificity 0.969). Thus, the AACC double genotype of CD147 and DRB1*1501 polymorphisms seems to be a clinically highly specific marker of severity, systemic therapy and radiotherapy of patients with T-cell lymphoma. Conclusion: Although genotyping results were not known during the treatment decision and could not modify it, the clinical decision on severity and therapy reflected some aspects of the genetic background of this complicated T-cell-associated disease very well.
ER  -

VAŠKŮ, Vladimír, Petra FIALOVÁ and Anna VAŠKŮ. New Genetic Markers of Skin T-Cell Lymphoma Treatment. \textit{GENES}. BASEL: MDPI, 2024, vol.~15, No~3, p.~1-9. ISSN~2073-4425. Available from: https://dx.doi.org/10.3390/genes15030358.

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