microRNA expression in acute myeloid leukaemia: New targets for therapy?

Fletcher, Daniel; Brown, Elliott C.; Javadala, Julliah; Uysal‐Onganer, Pinar; Guinn, Barbara

doi:10.1002/jha2.441

Cited by 10 publications

(7 citation statements)

References 124 publications

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“…Recent studies have implicated several microRNAs (miRNAs) in AML pathogenesis, including hsa-miR-192, hsa-miR-221, and hsa-miR-21. These miRNAs are dysregulated in AML patients and may affect disease progression and treatment response ( Wallace and O'Connell, 2017 , Fletcher et al, 2022 ). Our results agree with the results of the present study.…”

Section: Discussionmentioning

confidence: 99%

Exploring the interplay between microRNA expression and DNA mutation analysis in AML patients

Saeed,

Faqe Ahmed Abdulrahman,

Mohammad

2024

Saudi Journal of Biological Sciences

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Section: Discussionmentioning

confidence: 99%

Exploring the interplay between microRNA expression and DNA mutation analysis in AML patients

Saeed,

Faqe Ahmed Abdulrahman,

Mohammad

2024

Saudi Journal of Biological Sciences

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“…TP53 has been examined as a target for the treatment of AML using microRNA (miRNA) therapy, including miR-223, which is currently in preclinical trials. Despite there being little data on miRNA therapy in AML, the fact that miR-223 has been linked to all FAB subtypes does give promise that, with the correct delivery system, it could provide an effective targeted treatment for a wide range of patients [94]. Similarly to other targeting techniques, toxicity issues would need to be addressed, which is where both delivery system and potential combinational approaches would need careful consideration.…”

Section: Discussionmentioning

confidence: 99%

A Direct Comparison, and Prioritisation, of the Immunotherapeutic Targets Expressed by Adult and Paediatric Acute Myeloid Leukaemia Cells: A Systematic Review and Meta-Analysis

Morris

Ghazi

Fletcher

et al. 2023

IJMS

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Acute myeloid leukaemia (AML) is characterized by impaired myeloid differentiation resulting in an accumulation of immature blasts in the bone marrow and peripheral blood. Although AML can occur at any age, the incidence peaks at age 65. The pathobiology of AML also varies with age with associated differences in incidence, as well as the frequency of cytogenetic change and somatic mutations. In addition, 5-year survival rates in paediatrics are 60–75% but fall to 5–15% in older AML patients. This systematic review aimed to determine whether the altered genes in AML affect the same molecular pathways, indifferent of patient age, and, therefore, whether patients could benefit from the repurposing drugs or the use of the same immunotherapeutic strategies across age boundaries to prevent relapse. Using a PICO framework and PRISMA-P checklist, relevant publications were identified using five literature databases and assessed against an inclusion criteria, leaving 36 articles, and 71 targets for therapy, for further analysis. QUADAS-2 was used to determine the risk of bias and perform a quality control step. We then priority-ranked the list of cancer antigens based on predefined and pre-weighted objective criteria as part of an analytical hierarchy process used for dealing with complex decisions. This organized the antigens according to their potential to act as targets for the immunotherapy of AML, a treatment that offers an opportunity to remove residual leukaemia cells at first remission and improve survival rates. It was found that 80% of the top 20 antigens identified in paediatric AML were also within the 20 highest scoring immunotherapy targets in adult AML. To analyse the relationships between the targets and their link to different molecular pathways, PANTHER and STRING analyses were performed on the 20 highest scoring immunotherapy targets for both adult and paediatric AML. There were many similarities in the PANTHER and STRING results, including the most prominent pathways being angiogenesis and inflammation mediated by chemokine and cytokine signalling pathways. The coincidence of targets suggests that the repurposing of immunotherapy drugs across age boundaries could benefit AML patients, especially when used in combination with conventional therapies. However, due to cost implications, we would recommend that efforts are focused on ways to target the highest scoring antigens, such as WT1, NRAS, IDH1 and TP53, although in the future other candidates may prove successful.

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“…Moreover, they have a unique molecular profile ( 61 ). AML-secreted exosomal miRNAs are involved in the progression of AML and can be used as entry points for AML treatment ( 86 , 87 ).…”

Section: Application Of Exosomes In the Diagnosis And Prognosis Of Amlmentioning

confidence: 99%

Utilizing exosomes as sparking clinical biomarkers and therapeutic response in acute myeloid leukemia

Wang,

Wu,

Zheng

et al. 2024

Front. Immunol.

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Acute myeloid leukemia (AML) is a malignant clonal tumor originating from immature myeloid hematopoietic cells in the bone marrow with rapid progression and poor prognosis. Therefore, an in-depth exploration of the pathogenesis of AML can provide new ideas for the treatment of AML. In recent years, it has been found that exosomes play an important role in the pathogenesis of AML. Exosomes are membrane-bound extracellular vesicles (EVs) that transfer signaling molecules and have attracted a large amount of attention, which are key mediators of intercellular communication. Extracellular vesicles not only affect AML cells and normal hematopoietic cells but also have an impact on the bone marrow microenvironment and immune escape, thereby promoting the progression of AML and leading to refractory relapse. It is worth noting that exosomes and the various molecules they contain are expected to become the new markers for disease monitoring and prognosis of AML, and may also function as drug carriers and vaccines to enhance the treatment of leukemia. In this review, we mainly summarize to reveal the role of exosomes in AML pathogenesis, which helps us elucidate the application of exosomes in AML diagnosis and treatment.

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microRNA expression in acute myeloid leukaemia: New targets for therapy?

Cited by 10 publications

References 124 publications

Exploring the interplay between microRNA expression and DNA mutation analysis in AML patients

Exploring the interplay between microRNA expression and DNA mutation analysis in AML patients

A Direct Comparison, and Prioritisation, of the Immunotherapeutic Targets Expressed by Adult and Paediatric Acute Myeloid Leukaemia Cells: A Systematic Review and Meta-Analysis

Utilizing exosomes as sparking clinical biomarkers and therapeutic response in acute myeloid leukemia

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