Proteomics for optimizing therapy in acute myeloid leukemia: venetoclax plus hypomethylating agents versus conventional chemotherapy.
Leukemia
; 38(5): 1046-1056, 2024 May.
Article
en En
| MEDLINE
| ID: mdl-38531950
ABSTRACT
The use of Hypomethylating agents combined with Venetoclax (VH) for the treatment of Acute Myeloid Leukemia (AML) has greatly improved outcomes in recent years. However not all patients benefit from the VH regimen and a way to rationally select between VH and Conventional Chemotherapy (CC) for individual AML patients is needed. Here, we developed a proteomic-based triaging strategy using Reverse-phase Protein Arrays (RPPA) to optimize therapy selection. We evaluated the expression of 411 proteins in 810 newly diagnosed adult AML patients, identifying 109 prognostic proteins, that divided into five patient expression profiles, which are useful for optimizing therapy selection. Furthermore, using machine learning algorithms, we determined a set of 14 proteins, among those 109, that were able to accurately recommend therapy, making it feasible for clinical application. Next, we identified a group of patients who did not benefit from either VH or CC and proposed target-based approaches to improve outcomes. Finally, we calculated that the clinical use of our proteomic strategy would have led to a change in therapy for 30% of patients, resulting in a 43% improvement in OS, resulting in around 2600 more cures from AML per year in the United States.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sulfonamidas
/
Leucemia Mieloide Aguda
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Protocolos de Quimioterapia Combinada Antineoplásica
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Compuestos Bicíclicos Heterocíclicos con Puentes
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Proteómica
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Leukemia
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
Año:
2024
Tipo del documento:
Article
País de afiliación:
Países Bajos