The Potential of Exosomes Derived from Chronic Myelogenous Leukaemia Cells as a Biomarker

Kang, Ka-Won; Jung, Jik Han; Hur, Woojune; Park, Jaena; Shin, Hyunku; Choi, Byeonghyeon; Jeong, Hyesun; Kim, Dae Sik; Yu, Eun-Jeong; Lee, Se Ryeon; Sung, Hwa Jung; Kim, Seok Jin; Choi, Chul Won; Kim, Hyun Koo; Hong, Sunghoi; Park, Ji Ho; Choi, Yeonho; Park, Yong

doi:10.21873/anticanres.12679

Cited by 23 publications

(33 citation statements)

References 27 publications

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“…1 monitored from diagnosis to the achievement of the dMR) the exosome enrichment performed using the SoRTEV™ EV-RNA Low Volume Enrichment kit highlighted the presence of the BCR-ABL1 transcript in leukemia-derived EVs. A previous study demonstrated the detectability of this fusion gene transcript in the total exosomes pool of patients affected by cML, not enriched for specific sub-populations; BCR-ABL1 was only detected by conventional nested PcR in patients in the accelerated phase or in blast crisis (44). These results contradict those of the present study, which may be due to the improvements in the specificity of leukemia-derived exosome enrichment methods combined with highly sensitive dPCR quantification.…”

Section: Discussioncontrasting

confidence: 99%

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Feasibility of tumor‑derived exosome enrichment in the onco‑hematology leukemic model of chronic myeloid leukemia

et al. 2019

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due to the discovery of their role in intra-cellular communications, exosomes, which carry information specific to the cell of origin, have garnered considerable attention in cancer research. Moreover, there is evidence to suggest the possibility of isolating different exosome sub-populations based on target antigens at the cell surface. Philadelphia chromosome-positive (Ph +) chronic myeloid leukemia (cML) is a clonal myeloproliferative neoplasia characterized by the breakpoint cluster region-proto-oncogene 1 tyrosine-protein kinase (BcR-ABL1) fusion-gene, derived from the t (9;22) translocation. Tyrosine kinase inhibitors (TKIs) target BcR-ABL1 protein and induce major or deep molecular responses in the majority of patients. despite the fact that several studies have demonstrated the persistence of leukemic cells in the bone marrow niche, even following treatment, TKIs prolong patient survival time and facilitate treatment-free remission. These characteristics render cML a plausible model for investigating the feasibility of tumor-derived exosome fraction enrichment. In the present study, patients in the chronic phase (cP) of CML were treated with TKIs, and the quantification of the BCR-ABL1 exosomal transcript was performed using digital PcR (dPcR). The possibility of tumor-derived exosomes enrichment was confirmed, and for the first time, to the best of our knowledge, the detection of the BcR-ABL1 transcript highlighted the presence of active leukemic cells in patients with CP-CML. According to these findings, tumor-derived exosomes may be considered a novel tool for the identification of active leukemic cells, and for the assessment of innovative monitoring focused on the biological functions of exosomes in cML.

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Section: Discussioncontrasting

confidence: 99%

“…Specifically, a previous study demonstrated the possibility of quantifying the BCR-ABL1 transcript in exosomes isolated from the PB of patients with cML in advanced disease phases, such as accelerating or blast phases. However, they were not be able to detect BCR-ABL1 by nested PcR in cML patients in the cP (44).…”

Section: Discussionmentioning

confidence: 85%

Feasibility of tumor‑derived exosome enrichment in the onco‑hematology leukemic model of chronic myeloid leukemia

et al. 2019

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“…Moreover, changes in absolute EV counts and EV protein contents have been observed after induction chemotherapy and corresponded to blast reduction in the BM (117,119). Furthermore, EVs from malignant cells express abundant surface proteins unique to their cell of origin (120). For example, EVs derived from multiple myeloma cells overexpress, on their cell membrane, proteins such as CD147, CD38, and CD138 (115,(121)(122)(123).…”

Section: Ev Applications In Promoting Gvl and In Preventing Disease Rmentioning

confidence: 99%

Extracellular Vesicles After Allogeneic Hematopoietic Cell Transplantation: Emerging Role in Post-Transplant Complications

et al. 2020

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Extracellular vesicles (EVs) play an important role in the cellular crosstalk by transferring bioactive molecules through biological barriers from a cell to another, thus influencing recipient cell functions and phenotype. Therefore, EVs are increasingly being explored as biomarkers of disease progression or response to therapy and as potential therapeutic agents in different contexts including in hematological malignancies. Recently, an EV role has emerged in allogeneic hematopoietic cell transplantation (allo-HCT) as well. Allogeneic hematopoietic cell transplantation often represents the only curative option in several hematological disorders, but it is associated with potentially life-threatening complications that can have a significant impact on clinical outcomes. The most common complications have been well-established and include graft-versus-host disease and infections. Furthermore, relapse remains an important cause of treatment failure. The aim of this review is to summarize the current knowledge, the potential applications, and clinical relevance of EVs in allo-HCT. Herein, we will mainly focus on the immune-modulating properties of EVs, in particular those derived from mesenchymal stromal cells, as potential therapeutic strategy to improve allo-HCT outcome. Moreover, we will briefly describe the main findings on EVs as biomarkers to monitor graft-versushost disease onset and tumor relapse.

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“…Accessible, reliable, and informative hematological malignancies biomarkers can be medically valuable and can provide some relevant insights into cancer biology [Elsherbini and Bieberich., 2018]. Early detection of cancer could be easily performed using exosomes isolated from body fl uids such as blood plasma, serum, and urine, which is allowing for a non-invasive method of detection of hematological malignancies, (Kang et al, 2018).…”

Section: The Role Of Exosomes In Diagnosis and Prognosis Of Hematologmentioning

confidence: 99%

“…Microvesicles are found in higher concentrations in the sera of different types of hematological malignancies, such as AML, AL L, CML, CLL, diffuse large B-cell lymphoma ( DLBCL), Hodgkin's lymphoma (HL) and MM patients and abundantly express surface proteins unique to their cell of origin, which is rarely observed from serum microvesicles of normal controls [Kang et al, 2018]. AML biomarkers NPM1, FLT3, CXCR4, MMP9 and IGF-IR are also present in AML cell derived exosomes, along with mRNAs involved in leukemia development (Boyiadzis, 2016).…”

Section: The Role Of Exosomes In Diagnosis and Prognosis Of Hematologmentioning

confidence: 99%

The central roles of exosomes in hematological malignancies: A new frontier review

Xia¹,

Li²,

Yang³

et al. 2018

Biosci. Biotech. Res. Comm

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Exosomes, which are 30-to 120-nm vesicles, are released by most types of cells, including tumor cells. In hematological malignancies, exosome-mediated expulsion of a number of key proteins and micro RNAs, resulting in infl uence of major tumor-related pathways. Emerging evidence suggests that the component secreted by exosomescan promote tumor survival,angiogenesis and metastasis, and also mediate tumor microenvironment induced drug resistance and immune escape. Furthermore, exosomes contain a great variety of bioactive molecules and are emerging as rich reservoirs of hematological tumor-specifi c biomarkers for the detection and therapeutics.This comprehensive review highlights the advancements in understanding of the pathogenesis of exosomes secretion and the consequence onhematological malignancies development. Full knowledge of the contribution of exosomes to the potential medical application ofdiagnosis and treatment will depend on the ingenuity of future investigators and their insight into biological processes.

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The Potential of Exosomes Derived from Chronic Myelogenous Leukaemia Cells as a Biomarker

Abstract: CML-derived exosomes could act as novel targets for the detection of the BCR-ABL transcript.

Cited by 23 publications

References 27 publications

Feasibility of tumor‑derived exosome enrichment in the onco‑hematology leukemic model of chronic myeloid leukemia

Feasibility of tumor‑derived exosome enrichment in the onco‑hematology leukemic model of chronic myeloid leukemia

Extracellular Vesicles After Allogeneic Hematopoietic Cell Transplantation: Emerging Role in Post-Transplant Complications

The central roles of exosomes in hematological malignancies: A new frontier review

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