The role of autophagy in acute myeloid leukemia development

ABSTRACT

Introduction

Autophagy is a highly conservative self-degradative process. It aims at elimination-impaired proteins and cellular organelles. Previous research confirmed the autophagy role in cancer pathogenesis.

Areas covered

This article discusses the role of autophagy in the development of AML. Autophagy seems to be a ‘double-sword’ mechanism, hence, either its suppression or induction could promote neoplasm growth. This mechanism could also be the aim of the ‘molecular targeted therapy.’ Chemo- and radiotherapy induce cellular stress in neoplasm cells with subsequent autophagy suppression. Simultaneously, it is claimed that the autophagy suppression increases chemosensitivity ’in neoplastic cells. Some agents, like bortezomib, in turn could promote autophagy process, e.g. in AML (acute myeloid leukemia). However, currently there are not many studies focusing on the role of autophagy in patients suffering for AML. In this review, we summarize the research done so far on the role of autophagy in the development of AML.

Expert opinion

The analysis of autophagy genes expression profiling in AML could be a relevant factor in the diagnostic process and treatment ‘individualization.’ Autophagy modulation seems to be a relevant target in the oncological therapy – it could limit disease progression and increase the effectiveness of treatment.

KEYWORDS:

• Acute myeloid leukemia
• autophagy
• cancer
• hematology
• lysosome
• mitophagy
• myleloid
• proteasome

Article highlights

• autophagy plays a significant role in most pathological processes in the body, including cancer

• autophagy plays a dual role in cancer development, it can both inhibit and induce oncogenesis

• ATG5 and ATG7 deficiency resulted in a reduction in the incidence of HSC and progressed leukemia

• Loss of SQSTM1 (sequestosome 1), a selective autophagy receptor that binds to mitochondria and mediates mitophagy, induces the accumulation of damaged mitochondria, which interferes with the survival of leukemic cells

• In recent years, the expression of key genes related to autophagy (ATG7 and LC3) in AML patients has been assessed. Scientists sought to discover specific new ways of diagnosing, predicting, targeted therapy and monitoring the disease. The results showed a decrease in ATG7 and LC3 gene expression compared to the control group - loss of autophagy genes may promote tumor growth.

• Inhibition of autophagy in combination with traditional cytotoxic drugs increases the chemotherapeutic sensitivity in cancer cells, including AML.

• The regulation of the autophagy process can be used in the prevention and therapy of cancer by preventing the development of the disease, limiting the progression and increasing the effectiveness of treatment

• Modulation of autophagy increases therapeutic efficacy and combats drug resistance.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper received no funding.