Autophagy in acute myeloid leukemia: a paradoxical role in chemoresistance

Khan, Aafreen; Singh, Vivek Kumar; Thakral, Deepshi; Gupta, Ritu

doi:10.1007/s12094-022-02804-z

Cited by 7 publications

(4 citation statements)

References 74 publications

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“…Numerous tumor suppressor oncogenes have been identified as autophagic regulators, including the oncosuppressor p53, which may halt or induce autophagy depending on its cellular Pharmaceutics 2022, 14, 862 2 of 17 localization and the underlying signaling pathways [8]. Accumulating evidence shows that downregulating key autophagic genes correlates with the promotion of tumorigenesis in some solid tumors such as breast, ovarian and prostate cancers [9].…”

Section: Introductionmentioning

confidence: 99%

Squalene-Based Nano-Assemblies Improve the Pro-Autophagic Activity of Trehalose

Frapporti¹,

Colombo

Ahmed

et al. 2022

Pharmaceutics

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The disaccharide trehalose is a well-established autophagy inducer, but its therapeutic application is severely hampered by its low potency and poor pharmacokinetic profile. Thus, we targeted the rational design and synthesis of trehalose-based small molecules and nano objects to overcome such issues. Among several rationally designed trehalose-centered putative autophagy inducers, we coupled trehalose via suitable spacers with known self-assembly inducer squalene to yield two nanolipid-trehalose conjugates. Squalene is known for its propensity, once linked to a bioactive compound, to assemble in aqueous media in controlled conditions, internalizing its payload and forming nanoassemblies with better pharmacokinetics. We assembled squalene conjugates to produce the corresponding nanoassemblies, characterized by a hydrodynamic diameter of 188 and 184 nm and a high stability in aqueous media as demonstrated by the measured Z-potential. Moreover, the nanoassemblies were characterized for their toxicity and capability to induce autophagy in vitro.

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Section: Introductionmentioning

confidence: 99%

Squalene-Based Nano-Assemblies Improve the Pro-Autophagic Activity of Trehalose

Frapporti¹,

Colombo

Ahmed

et al. 2022

Pharmaceutics

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“…A widely accepted view is that autophagy serves as a quality control mechanism during the early stages of leukemia development, acting to suppress leukemia initiation. Should autophagy become impaired, it may drive the initiation and development of leukemia [ 20 ].…”

Section: Autophagy and Hematopoiesismentioning

confidence: 99%

Crosstalk between autophagy and metabolism: implications for cell survival in acute myeloid leukemia

Chen,

Zou

et al. 2024

Cell Death Discov.

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Acute myeloid leukemia (AML), a prevalent form of leukemia in adults, is often characterized by low response rates to chemotherapy, high recurrence rates, and unfavorable prognosis. A critical barrier in managing refractory or recurrent AML is the resistance to chemotherapy. Increasing evidence indicates that tumor cell metabolism plays a crucial role in AML progression, survival, metastasis, and treatment resistance. Autophagy, an essential regulator of cellular energy metabolism, is increasingly recognized for its role in the metabolic reprogramming of AML. Autophagy sustains leukemia cells during chemotherapy by not only providing energy but also facilitating rapid proliferation through the supply of essential components such as amino acids and nucleotides. Conversely, the metabolic state of AML cells can influence the activity of autophagy. Their mutual coordination helps maintain intrinsic cellular homeostasis, which is a significant contributor to chemotherapy resistance in leukemia cells. This review explores the recent advancements in understanding the interaction between autophagy and metabolism in AML cells, emphasizing their roles in cell survival and drug resistance. A comprehensive understanding of the interplay between autophagy and leukemia cell metabolism can shed light on leukemia cell survival strategies, particularly under adverse conditions such as chemotherapy. This insight may also pave the way for innovative targeted treatment strategies.

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“…During stressful situations like nutrition shortages and infections, autophagy, a highly conserved catabolic process, sends cytoplasmic proteins, damaged organelles, and microorganisms to lysosomes for breakdown (1) .…”

Section: Introductionmentioning

confidence: 99%

“…Numerous studies showed how the deletion of essential autophagy genes like TG7 or ATG5 in animal models disrupted the normal metabolic activity of HSCs, led to a buildup of mitochondrial superoxide, caused DNA damage, and encouraged a pre-leukemic state. Additionally, according to extensive genomic investigations of human tumours, oncogenic events that may activate autophagy have been seen, although deletion or mutation of essential autophagy genes is not prevalent (1)(2)(3) .…”

Section: Introductionmentioning

confidence: 99%

The Controversial Role of Autophagy in AML/ Cancer: Review Article

Morsy¹,

Zahran²,

Hassan

et al. 2022

The Egyptian Journal of Hospital Medicine

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Background: A catabolic process that has been preserved throughout evolution, autophagy sends cytoplasmic proteins, organelles, and bacteria to lysosomes for destruction. Within its subtypes, acute myeloid leukaemia (AML) exhibits a significant lot of variety, and autophagy's complex function in the disease's genesis and development is also evident. Chromosome translocations and rearrangements, which are often seen in AML, have been discovered to be related with heterozygous deletions and missense mutations of important autophagy genes. Objective: In this review we aimed to discuss the dual role of autophagy in cancer and focusing on the relation between autophagy and acute myeloid leukemia. Methods: PubMed, Google scholar and Science direct were searched using the following keywords: Autophagy, Cancer, Acute myeloid leukaemia and Chromosomal translocations. The authors also screened references from the relevant literature, including all the identified studies and reviews, only the most recent or complete study was included between December 2001 and May 2022. Documents in a language apart from English have been excluded as sources for interpretation. Papers apart from main scientific studies had been excluded as well as documents unavailable as total written text, conversation, conference abstract papers and dissertations. Conclusion:It is now understood that the process of autophagy has a dual role in the initiation and progression of cancer. In terms of using autophagy in modern treatment modalities like cancer immunotherapy and precision medicine in AML, this might be advantageous. Additionally, the utilization of autophagy biomarkers for clinical response and therapeutic effectiveness prediction would eventually result in better results and the best possible care for AML patients.

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Autophagy in acute myeloid leukemia: a paradoxical role in chemoresistance

Cited by 7 publications

References 74 publications

Squalene-Based Nano-Assemblies Improve the Pro-Autophagic Activity of Trehalose

Squalene-Based Nano-Assemblies Improve the Pro-Autophagic Activity of Trehalose

Crosstalk between autophagy and metabolism: implications for cell survival in acute myeloid leukemia

The Controversial Role of Autophagy in AML/ Cancer: Review Article

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