Cross-sectional network analysis of plasma proteins/metabolites correlated with pathogenesis and therapeutic response in acute promyelocytic leukemia.
Front Med
; 18(2): 327-343, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38151667
ABSTRACT
The treatment of PML/RARA+ acute promyelocytic leukemia (APL) with all-trans-retinoic acid and arsenic trioxide (ATRA/ATO) has been recognized as a model for translational medicine research. Though an altered microenvironment is a general cancer hallmark, how APL blasts shape their plasma composition is poorly understood. Here, we reported a cross-sectional correlation network to interpret multilayered datasets on clinical parameters, proteomes, and metabolomes of paired plasma samples from patients with APL before or after ATRA/ATO induction therapy. Our study revealed the two prominent features of the APL plasma, suggesting a possible involvement of APL blasts in modulating plasma composition. One was characterized by altered secretory protein and metabolite profiles correlating with heightened proliferation and energy consumption in APL blasts, and the other featured APL plasma-enriched proteins or enzymes catalyzing plasma-altered metabolites that were potential trans-regulatory targets of PML/RARA. Furthermore, results indicated heightened interferon-gamma signaling characterizing a tumor-suppressing function of the immune system at the first hematological complete remission stage, which likely resulted from therapy-induced cell death or senescence and ensuing supraphysiological levels of intracellular proteins. Overall, our work sheds new light on the pathophysiology and treatment of APL and provides an information-rich reference data cohort for the exploratory and translational study of leukemia microenvironment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
1_ASSA2030
Problema de saúde:
1_geracao_evidencia_conhecimento
Assunto principal:
Tretinoína
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Proteínas Sanguíneas
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Leucemia Promielocítica Aguda
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Trióxido de Arsênio
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Front Med
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China