Mitochondria as emerging targets for therapies against T cell acute lymphoblastic leukemia.
J Leukoc Biol
; 105(5): 935-946, 2019 05.
Article
em En
| MEDLINE
| ID: mdl-30698851
ABSTRACT
Acute lymphoblastic leukemia (ALL) comprises a heterogeneous group of hematologic malignancies, arising from diverse genetic alterations in the early lymphocyte development. T-cell subtype of ALL (T-ALL) accounts for about 15% and 25% of ALL in children and adults, respectively. Being less frequent among ALL subtypes, T-ALL represents a high-risk factor for poor prognosis due to its aggressiveness and resistance to common antileukemic drugs. Mitochondria were widely explored recently as a target for anticancer treatment because they are involved in a metabolic reprogramming of a cancer cell and play key roles in reactive oxygen species generation, Ca2+ signaling, and cell death induction. Accordingly, a new class of anticancer compounds named mitocans has been developed, which target mitochondria at distinct crucial points to promote their dysfunction and subsequent cell death. The present review analyses the role of mitochondria in malignant reprogramming and emerging therapeutic strategies targeting mitochondria as an "Achilles' heel" in T-ALL, with an emphasis on BH3 mimetics, sequestering pro-survival BCL proteins and voltage-dependent anion channel (VDAC)1-directed drugs, which promote the suppression of aerobic glycolysis, VDAC1 closure, mitochondrial Ca2+ overload, stoppage of the oxidative phosphorylation, oxidative stress, and release of proapoptotic factors.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Prevencao_e_fatores_de_risco
/
Agentes_cancerigenos
/
Tipos_de_cancer
/
Leucemia
Base de dados:
MEDLINE
Assunto principal:
Regulação Leucêmica da Expressão Gênica
/
Proteínas Reguladoras de Apoptose
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Canal de Ânion 1 Dependente de Voltagem
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Leucemia-Linfoma Linfoblástico de Células Precursoras
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Mitocôndrias
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Child
/
Humans
Idioma:
En
Revista:
J Leukoc Biol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
México