CCL

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001-es BibID:BIBFORM111494
035-os BibID:(WoS)000958273300001 (Scopus)85151466619 (cikkazonosító)5802
Első szerző:Kotmayer Lili
Cím:Landscape of BCL2 Resistance Mutations in a Real-World Cohort of Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia Treated with Venetoclax / Lili Kotmayer, Tamás László, Gábor Mikala, Richárd Kiss, Luca Lévay, Lajos László Hegyi, Stefánia Gróf, Tibor Nagy, Gábor Barna, Péter Farkas, Júlia Weisinger, Zsolt Nagy, Alexandra Balogh, Tamás Masszi, Judit Demeter, Adrienn Sulák, Zoltán Kohl, Hussain Alizadeh, Miklós Egyed, Piroska Pettendi, Lajos Gergely, Márk Plander, Zsolt Pauker, András Masszi, András Matolcsy, Róbert Szász, Csaba Bödör, Donát Alpár
Dátum:2023
ISSN:1422-0067
Megjegyzések:The oral, highly selective Bcl2 inhibitor venetoclax has substantially improved the therapeutic landscape of chronic lymphocytic leukemia (CLL). Despite the remarkable response rates in patients with relapsed/refractory (R/R) disease, acquired resistance is the leading cause of treatment failure, with somatic BCL2 mutations being the predominant genetic drivers underpinning venetoclax resistance. To assess the correlation between disease progression and the most common BCL2 mutations G101V and D103Y, sensitive (10?4) screening for the most common BCL2 mutations G101V and D103Y was performed in 67 R/R CLL patients during venetoclax single-agent or venetoclax?rituximab combination therapy. With a median follow-up time of 23 months, BCL2 G101V and D103Y were detected in 10.4% (7/67) and 11.9% (8/67) of the cases, respectively, with four patients harboring both resistance mutations. Ten out of eleven patients carrying BCL2 G101V and/or D103Y experienced relapse during the follow-up period, representing 43.5% of the cases (10/23) showing clinical signs of disease progression. All BCL2 G101V or D103Y variants were detected in patients receiving venetoclax as a continuous single-agent treatment while these mutations were not observed during or after fixed-duration venetoclax therapy. Targeted ultra-deep sequencing of BCL2 uncovered three additional variants in four patient samples obtained at relapse, suggesting convergent evolution and implying a cooperating role of BCL2 mutations in driving venetoclax resistance. This cohort is the largest R/R CLL patient population reported to date in which BCL2 resistance mutations were investigated. Our study demonstrates the feasibility and clinical value of sensitive screening for BCL2 resistance mutations in R/R CLL.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
CLL
venetoclax
BCL2
therapy resistance
molecular monitoring
Megjelenés:International Journal Of Molecular Sciences. - 24 : 6 (2023), p. 1-15. -
További szerzők:László Tamás Mikala Gábor Kiss Richárd Lévay Luca Hegyi Lajos László Gróf Stefánia Nagy Tibor (1988-) (vegyész) Barna Gábor Farkas Péter Weisinger Júlia Nagy Zsolt Balogh Alexandra Masszi Tamás Demeter Judit Sulák Adrienn Kohl Zoltán Alizadeh, Hussain Egyed Miklós Pettendi Piroska Gergely Lajos (1965-) (belgyógyász, haematológus) Plander Márk Pauker Zsolt Masszi András Matolcsy András Szász Róbert (1972-) (belgyógyász, haematológus) Bödör Csaba Alpár Donát
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