| Autor: |
Carrillo-Tornel, Salvador, Chen-Liang, Tzu Hua, Zurdo, María, Puiggros Metje, Anna Maria, Gómez-Llonín, Andrea, García-Malo, María Dolores, Cuenca-Zamora, Ernesto José, Ortuño, Francisco José, Hurtado López, Ana María, Espinet Solà, Blanca, Jerez, Andrés |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Popis: |
[AHEAD] Data de publicació electrónica: 27-12-2022 Studies prior to next-generation sequencing (NGS) showed that the frequent indolent course of chronic lymphocytic leukaemia (CLL) is related to most cells remaining quiescent in the G0 -G1 cell cycle phase, due to the expression of dysregulated cyclin genes. Of note, the activating nature of the NOTCH1 mutation in T lymphoblastic leukaemia also drives the dysregulation of cell cycle genes. Our goal was to comprehensively revisit the cell cycle in NOTCH1-mutated CLL (NOTCH1MUT ) to test for potential therapeutic targets. Among 378 NGS-annotated CLL cases, NOTCH1MUT cells displayed a unique transcriptome profile of G0 -G1 cell cycle components, with an overexpression of early-phase effectors, reaching a 38-, 27- and ninefold change increase for the complex elements CCND3, CDK4 and CDK6, respectively. This NOTCH1MUT cells' profile was related to more cells traversing through the cell cycle. In-vitro targeted inhibition of NOTCH1 gamma-secretase and CDK4/6 reversed the distribution of cells through the cycle phases and enhanced the killing of NOTCH1MUT CLL cells, suggesting new therapeutic approaches. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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