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Molecular markers associated with clinical response to bexarotene therapy in cutaneous T-cell lymphoma
Annamari Ranki1, Liisa Väkevä, Laura Sipilä
1Department of Dermatology and Allergic Diseases, University of Helsinki, Finland. annamari.ranki@hus.fi
Abstract:
Bexarotene (Targretin(®)), was registered for the treatment of cutaneous T-cell lymphoma (CTCL) in 2002, and has been reported to induce a 45% overall response. Responses are mostly partial or generate a stable, skin-restricted disease. This study explored the usefulness of a novel cancer-associated gene, NAV3 and corresponding chromosome 12 copy numbers as possible biomarkers to monitor the therapeutic response to bexarotene in 21 Finnish patients with CTCL. Six patients (29%) reached complete remission (CR) and 3 of these remained in CR for more than 24 months, 12 (57%) reached a partial response (PR, with one stable disease) and 3 were non-responders. Low-level NAV3 deletions were detected using a fluorescence in-situ hybridization (FISH) assay in the lesions of 5 patients, 4 of whom were non-responders or progressed after short PR. This occurrence of NAV3 deletions was statistically significant compared with non-progressors (p = 0.011, Fisher's exact test). Chromosome 12 tetraploidy was found in the lesions of two of the 3 patients with CR who remained in remission. While such tetraploidy is a feature of proliferating normal T cells, this observation may reflect a favourable anti-tumour immune response among the skin-infiltrating lymphocytes.
Insights
NAV3 gene deletions in cutaneous T-cell lymphoma (CTCL) lesions indicate poor response to bexarotene therapy. Conversely, chromosome 12 tetraploidy may signal a favorable anti-tumor immune response in patients achieving remission.
Area of Science:
- Oncology
- Genetics
- Immunology
Background:
- Bexarotene is approved for cutaneous T-cell lymphoma (CTCL), with variable response rates.
- Monitoring therapeutic response in CTCL remains a clinical challenge.
Purpose of the Study:
- To investigate NAV3 gene copy number and chromosome 12 alterations as biomarkers for bexarotene treatment response in CTCL patients.
- To correlate genetic findings with clinical outcomes in a Finnish CTCL cohort.
Main Methods:
- Analysis of 21 Finnish CTCL patients treated with bexarotene.
- Fluorescence in-situ hybridization (FISH) assay to detect NAV3 deletions.
- Assessment of chromosome 12 copy numbers in tumor lesions.
Main Results:
- NAV3 deletions were significantly associated with non-response or disease progression (p = 0.011).
- Four out of five patients with NAV3 deletions were non-responders or progressed.
- Chromosome 12 tetraploidy was observed in patients with sustained complete remission.
Conclusions:
- NAV3 deletions may serve as a predictive biomarker for poor bexarotene response in CTCL.
- Chromosome 12 tetraploidy might indicate a favorable immune response in CTCL patients achieving remission.