Mitochondria as emerging targets for therapies against Tcell acute lymphoblastic leukemia

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Miguel Olivas-Aguirre¹  Igor Pottosin¹  Oxana Dobrovinskaya¹ 

[1] Laboratory of Immunobiology and Ionic Transport Regulation, University Center for Biomedical Research, University of Colima

关键词: apoptosis;    calcium;    cancer;    mitocans;    mitochondria;    ROS;    T cell acute lymphoblastic leukemia;   

DOI  :  10.1002/JLB.5VMR0818-330RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

CC BY