Feasibility of Leukemia-Derived Exosome Enrichment and Co-isolated dsDNA Sequencing in Acute Myeloid Leukemia Patients: A Proof of Concept for New Leukemia Biomarkers Detection

Bernardi, Simona; Farina, Mirko; Bosio, Katia; Lucanardo, Anna Di; Lanza, Antonio; Re, Federica; Polverelli, Nicola; Turra, Alessandro; Morello, Enrico; Buttini, Eugenia Accorsi; Zollner, Tatiana; Bonvicini, Cristian; Malagola, Michele; Russo, Domenico

doi:10.3390/cancers14184504

Cited by 7 publications

(4 citation statements)

References 60 publications

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“…Therefore, the use of cfDNA may increase the sensitivity of peripheral blood for detection of MRD. Studies have shown that the use of extracellular vesicles obtained from PB samples can be used for the detection of prognostic and follow-up biomarkers in AML ( 33 – 38 ). In general, bone marrow was studied because it increases sensitivity by at least one logarithm versus peripheral blood for MRD evaluation in AML.…”

Section: Discussionmentioning

confidence: 99%

Detection of minimal residual disease in acute myeloid leukemia: evaluating utility and challenges

Álvarez,

Martín,

Dorado

et al. 2024

Front. Immunol.

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This study discusses the importance of minimal residual disease (MRD) detection in acute myeloid leukemia (AML) patients using liquid biopsy and next-generation sequencing (NGS). AML prognosis is based on various factors, including genetic alterations. NGS has revealed the molecular complexity of AML and helped refine risk stratification and personalized therapies. The long-term survival rates for AML patients are low, and MRD assessment is crucial in predicting prognosis. Currently, the most common methods for MRD detection are flow cytometry and quantitative PCR, but NGS is being incorporated into clinical practice due to its ability to detect genomic aberrations in the majority of AML patients. Typically, bone marrow samples are used for MRD assessment, but using peripheral blood samples or liquid biopsies would be less invasive. Leukemia originates in the bone marrow, along with the cfDNA obtained from peripheral blood. This study aimed to assess the utility of cell-free DNA (cfDNA) from peripheral blood samples for MRD detection in AML patients. A cohort of 20 AML patients was analyzed using NGS, and a correlation between MRD assessment by cfDNA and circulating tumor cells (CTCs) in paired samples was observed. Furthermore, a higher tumor signal was detected in cfDNA compared to CTCs, indicating greater sensitivity. Challenges for the application of liquid biopsy in MRD assessment were discussed, including the selection of appropriate markers and the sensitivity of certain markers. This study emphasizes the potential of liquid biopsy using cfDNA for MRD detection in AML patients and highlights the need for further research in this area.

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Section: Discussionmentioning

confidence: 99%

Detection of minimal residual disease in acute myeloid leukemia: evaluating utility and challenges

Álvarez,

Martín,

Dorado

et al. 2024

Front. Immunol.

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“…Plasma exosomal lncRNAs are potential cell-free indicators for the diagnosis and therapeutic monitoring of AML and offer novel and cutting-edge concepts for the liquid biopsy of hematologic cancers (98). Bernardi et al first used the commercially available CE-IVD-based kits for exosome-enrichment methods to investigate leukemic sources and exosomal dsDNA target resequencing for adult AML marker detection; they performed next-generation sequencing analysis of exosome-derived dsDNA isolated from 14 adult patients with AML and identified the optimal amount of exosomal dsDNA as a potential AML biomarker for liquid biopsies; they found exosomal dsDNA can be developed as a tool that can facilitate the monitoring of AML progression and the early diagnosis of relapse after allogeneic hematopoietic stem cell transplantation (99). In summary, exosomes may offer a novel perspective on AML diagnosis and treatment response (Table 2).…”

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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“…[50][51][52] Last but not least, the application of dPCR resulted able to performing a precise, sensitive, and accurate quantification of BCR::ABL1 transcripts shuttled by circulating extracellular vesicles, 53,54 similar to what was observed in another type of leukemia. [55][56][57] Considering these encouraging results, it is not surprising that new commercial assays have become available for BCR::ABL1 transcript detection by dPCR 58 and that coordinated multicentric studies are optimizing and standardizing CML MRD monitoring by dPCR. 59,60 These data are constantly confirmed by new evidence and altogether stress the utility of moving to dPCR for minimal residual disease (MRD) monitoring in CML patients, in particular in subjects presenting low levels of BCR::ABL1 transcript and potentially eligible for stopping TKI therapy.…”

Section: Toward the Identification Of The Best Candidates For Tfrmentioning

confidence: 99%

“… 50 – 52 Last but not least, the application of dPCR resulted able to performing a precise, sensitive, and accurate quantification of BCR::ABL1 transcripts shuttled by circulating extracellular vesicles, 53 , 54 similar to what was observed in another type of leukemia. 55 – 57 …”

Section: Toward the Identification Of The Best Candidates For Tfrmentioning

confidence: 99%

Twenty years of evolution of CML therapy: how the treatment goal is moving from disease to patient

Russo,

Malagola,

Polverelli

et al. 2023

Therapeutic Advances in Hematology

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The introduction of imatinib in 2000 opened the era of tyrosine kinase inhibitors (TKIs) for CML therapy and has revolutionized the life expectancy of CML patients, which is now quite like the one of the healthy aged population. Over the last 20 years, both the TKI therapy itself and the objectives have undergone evolutions highlighted and discussed in this review. The main objective of the CML therapy in the first 10 years after TKI introduction was to abolish the disease progression from the chronic to the blastic phase and guarantee the long-term survival of the great majority of patients. In the second 10 years (from 2010 to the present), the main objective of CML therapy moved from survival, considered achieved as a goal, to treatment-free remission (TFR). Two phenomena emerged: no more than 50–60% of CML patients could be candidates for discontinuation and over 50% of them molecularly relapse. The increased cumulative incidence of specific TKI off-target side effects was such relevant to compel to discontinue or reduce the TKI administration in a significant proportion of patients and to avoid a specific TKI in particular settings of patients. Therefore, the treatment strategy must be adapted to each category of patients. What about the patients who do not get or fail the TFR? Should they be compelled to continue the TKIs at the maximum tolerated dose? Alternative strategies based on the principle of minimal effective dose have been tested with success and they are now re-evaluated with more attention, since they guarantee survival and probably a better quality of life, too. Moving from treating the disease to treating the patient is an important change of paradigm. We can say that we are entering a personalized CML therapy, which considers the patients’ age, their comorbidities, tolerability, and specific objectives. In this scenario, the new techniques supporting the monitoring of the patients, such as the digital PCR, must be considered. In the present review, we present in deep this evolution and comment on the future perspectives of CML therapy.

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Feasibility of Leukemia-Derived Exosome Enrichment and Co-isolated dsDNA Sequencing in Acute Myeloid Leukemia Patients: A Proof of Concept for New Leukemia Biomarkers Detection

Cited by 7 publications

References 60 publications

Detection of minimal residual disease in acute myeloid leukemia: evaluating utility and challenges

Detection of minimal residual disease in acute myeloid leukemia: evaluating utility and challenges

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

Twenty years of evolution of CML therapy: how the treatment goal is moving from disease to patient

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