| Autor: |
S., Karpe, M., Artesi, J., Wayet, K., Durkin, V., Hahaut, K., Uchimaru, J., Makiyama, M., Iwanaga, A., Utsunomiya, P., Martijn Kolijn, A. W., Langerak, A., Burny, T., Watanabe, M., Georges, A., Van den Broeke |
| Zdroj: |
AIDS Reviews; 2023 Supplement, Vol. 25, p19-19, 1p |
| Abstrakt: |
Objectives Adult T-cell leukemia (ATL) is a treatment refractory aggressive T-cell malignancy affecting ~ 5% of Human T-cell Leukemia Virus-1 (HTLV-1) carriers after decades of asymptomatic infection. Asymptomatic carriers (ACs) carry multiple T-cell clones, each characterized by a unique proviral integration site (IS) in the host genome, whereas ATLs generally harbour a single dominant clone. Only ~ 20% of "high-risk ACs", identified based on high proviral load (PVL, ≥ 4 HTLV-1 copies/100 PBMCs), the prognostic marker in place, will progress to ATL. Hence, a molecular tool that can better risk-stratify ACs is urgently needed. Our group has developed a NGS method ("clonality") for quantifying the clonal distribution of ISs, which has proven useful to monitor the evolution of ATL and response to treatment. We hypothesized that clonality NGS can be used to identify the premalignant stage of ATL by detecting the dominant tumor precursor clone many years prior to the onset of symptoms. Methods We applied our viral clonality NGS method to longitudinal samples of a unique cohort of HTLV-1-ACs (JSPFAD, Japan) to examine the clonal landscape of high PVL ACs who subsequently developed ATL and compared these with high and low PVL ACs who did not develop malignancy, followed over an equivalent period. Results We established a metric for quantification of clonality and explored the association between our clonality score (VCE) and the patients' clinical outcome many years later. We found that i) VCE outperforms PVL in identifying ACs at high risk of progression, with zero false positives, resulting in better risk-stratification, ii) clonality better discriminates ACs from patients with smoldering ATL, iii) clonality prognostic performance is unaffected by low PVL or multiple ISs within a predominant T-cell clone as determined by TCRB NGS in > 30% of progressors. Conclusions Monitoring clonality signatures in ACs will allay unwarranted anxiety in 80% high-risk ACs who will not progress to ATL and allow individuals with increased risk to be better managed presumptively. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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