Targeting autophagy in multiple myeloma

Yun, Zhong; Zhichao, Jin; Hao, Yanling; Jiang, Ou; Yang, Rulai; Dong, Wen; Shen, Qun

doi:10.1016/j.leukres.2017.06.002

Cited by 47 publications

(45 citation statements)

References 72 publications

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“…Literature data focus on autophagy as an MM prosurvival mechanism able to exert a protective effect under drug treatment in that drug-resistant MM cells can escape the toxic effect of drugs via autophagy [92] . Proteasome inhibitors, such as bortezomib and carfilzomib, are the first-line drug for MM treatment in both newly diagnosed and relapsed patients.…”

Section: Autophagy As Prosurvival Machinery In MMmentioning

confidence: 99%

Autophagy: A New Mechanism of Prosurvival and Drug Resistance in Multiple Myeloma

Desantis

Saltarella

Lamanuzzi

et al. 2018

Translational Oncology

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Autophagy is an intracellular self-degradative process that balances cell energy source and regulates tissue homeostasis. In physiological condition, autophagy funnels cytoplasmic constituents to autophagolysosomes for degradation and is an alternative way for cell-death behavior. Here, we inspected autophagy as a prosurvival mechanism essential for drug resistance in multiple myeloma (MM). Accordingly, autophagy inhibitors used in association to conventional anti-MM drugs might enforce the effect against resistant MM plasma cells and render autophagy a new therapeutic target.

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Section: Autophagy As Prosurvival Machinery In MMmentioning

confidence: 99%

Autophagy: A New Mechanism of Prosurvival and Drug Resistance in Multiple Myeloma

Desantis

Saltarella

Lamanuzzi

et al. 2018

Translational Oncology

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“…15 In MM, autophagy induced by chemotherapeutic drugs can either play a cytoprotective role, through relieving cellular stress caused by toxic insult, or play a cytotoxic role, through triggering autophagy-related cell death. 16 Moreover, previous studies have shown that Dex-induced cell death in lymphoid leukemia is mediated through the initiation of autophagy. Induction of autophagy is required for acute lymphoblastic leukemia cells to overcome glucocorticoid resistance.…”

Section: Introductionmentioning

confidence: 99%

miR-221/222-Mediated Inhibition of Autophagy Promotes Dexamethasone Resistance in Multiple Myeloma

et al. 2019

Molecular Therapy

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Inherent or acquired resistance to chemotherapeutic drugs is still an obstacle for the treatment of multiple myeloma (MM). MicroRNA dysregulation is related to the development of chemoresistance in cancers. However, its role in chemoresistance of MM is largely unknown. Here we demonstrated that miR-221/222 were upregulated in plasma cells from patients with MM, especially those with relapsed or refractory disease. Moreover, expression levels of miR-221/222 were inversely correlated with dexamethasone (Dex) sensitivity of human MM cell lines. Importantly, we found that Dex induced pro-death autophagy in MM cells and the inhibition of autophagy significantly decreased Dex-induced cell death. Mechanistically, autophagy-related gene 12 (ATG12) was identified as a novel target gene of miR-221/222, and miR-221/222 overexpression inhibited autophagy by directly targeting ATG12 and the p27 kip (p27)-mammalian target of rapamycin (mTOR) pathway. Indeed, Dex treatment decreased the expression of miR-221/222, thereby activating the ATG12/p27-mTOR autophagy-regulatory axis and inducing cell death in Dex-sensitive MM cells. Furthermore, both in vitro and in vivo results showed that the inhibitions of miR-221/222 increased the expression of ATG12 and p27 and functionally induced extended autophagy and cell death of MM cells. In conclusion, our findings demonstrated the crucial role of the miR-221/222-ATG12/p27-mTOR autophagy-regulatory axis in Dex resistance of MM, and they suggest potential prediction and treatment strategies for glucocorticoid resistance.

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“…Thus, activation of autophagic cell death may represent a promising approach for treatment of MM (32)(33)(34)(35)(36). Recent studies have demonstrated that autophagy mediates drug resistance in MM cells and leads to development of clinical complications for MM, while inhibition of autophagy may reverse the response to drugs (37,38). However, the clinical role, particularly the prognostic role of ARGs in MM, has yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

A predicted risk score based on the expression of 16 autophagy‑related genes for multiple myeloma survival

Zhu¹,

Wang

Zeng³

et al. 2019

Oncol Lett

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Autophagy has an important role in the pathogenesis of plasma cell development and multiple myeloma (MM); however, the prognostic role of autophagy-related genes (ARGs) in MM remains undefined. In the present study, the expression profiles of 234 ARGs were obtained from a Gene Expression Omnibus dataset (accession GSE24080), which contains 559 samples of patients with MM analyzed with 54,675 probes. Univariate Cox regression analysis identified 55 ARGs that were significantly associated with event-free survival of MM. Furthermore, a risk score with 16 survival-associated ARGs was developed using multivariate Cox regression analysis, including ATIC,

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Targeting autophagy in multiple myeloma

Cited by 47 publications

References 72 publications

Autophagy: A New Mechanism of Prosurvival and Drug Resistance in Multiple Myeloma

Autophagy: A New Mechanism of Prosurvival and Drug Resistance in Multiple Myeloma

miR-221/222-Mediated Inhibition of Autophagy Promotes Dexamethasone Resistance in Multiple Myeloma

A predicted risk score based on the expression of 16 autophagy‑related genes for multiple myeloma survival

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