Basic Knowledge on Bcr-Abl1-Positive Extracellular Vesicles

Jurj, Ancuța; Pașca, Sergiu; Teodorescu, Patric; Tomuleasa, Ciprian; Berindan‐Neagoe, Ioana

doi:10.2217/bmm-2019-0510

Cited by 8 publications

(10 citation statements)

References 57 publications

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“…CML EVs have been shown to promote leukemic growth in an autocrine manner [ 125 ], as well as promote and “transfer” resistance to tyrosine kinase inhibitors (TKIs), when released by imatinib-resistant cells [ 126 ]. CML-derived EVs contain BCR-ABL1 protein [ 127 ] and DNA [ 128 ] and can thus lead to development of CML-like disease, as shown after transfer to immunodeficient mice [ 128 ]. Similarly, AML-derived EVs have been shown to promote growth of leukemic cells, as well as transport molecules responsible for chemoresistance of AML cells [ 129 , 130 ].…”

Section: Leukemia-derived Factors That Promote Immune Evasionmentioning

confidence: 99%

Immunosuppressive Cell Subsets and Factors in Myeloid Leukemias

Swatler

Turos-Korgul

Kozłowska

et al. 2021

Cancers

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Both chronic myeloid leukemia and acute myeloid leukemia evade the immune response during their development and disease progression. As myeloid leukemia cells modify their bone marrow microenvironment, they lead to dysfunction of cytotoxic cells, such as CD8+ T cells or NK cells, simultaneously promoting development of immunosuppressive regulatory T cells and suppressive myeloid cells. This facilitates disease progression, spreading of leukemic blasts outside the bone marrow niche and therapy resistance. The following review focuses on main immunosuppressive features of myeloid leukemias. Firstly, factors derived directly from leukemic cells – inhibitory receptors, soluble factors and extracellular vesicles, are described. Further, we outline function, properties and origin of main immunosuppressive cells - regulatory T cells, myeloid derived suppressor cells and macrophages. Finally, we analyze interplay between recovery of effector immunity and therapeutic modalities, such as tyrosine kinase inhibitors and chemotherapy.

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Section: Leukemia-derived Factors That Promote Immune Evasionmentioning

confidence: 99%

Immunosuppressive Cell Subsets and Factors in Myeloid Leukemias

Swatler

Turos-Korgul

Kozłowska

et al. 2021

Cancers

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“…The role of BCR in not completely understood, but it has serine/threonine kinase activity and is a GTPase-activating protein. BCR-ABL1 fusion known as the Philadelphia chromosome that occurs due to a reciprocal translocation between chromosomes 9 and 22 is the driver fusion in chronic myeloid leukemia (CML) (Fu et al, 2017;Jurj et al, 2020). The fusion leads to dysregulation and overactivation of ABL1 tyrosine kinase domain.…”

Section: Bcr-abl1mentioning

confidence: 99%

Extracellular Vesicles: A Novel Tool Facilitating Personalized Medicine and Pharmacogenomics in Oncology

2021

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Biomarkers that can guide cancer therapy based on patients’ individual cancer molecular signature can enable a more effective treatment with fewer adverse events. Data on actionable somatic mutations and germline genetic variants, studied by personalized medicine and pharmacogenomics, can be obtained from tumor tissue or blood samples. As tissue biopsy cannot reflect the heterogeneity of the tumor or its temporal changes, liquid biopsy is a promising alternative approach. In recent years, extracellular vesicles (EVs) have emerged as a potential source of biomarkers in liquid biopsy. EVs are a heterogeneous population of membrane bound particles, which are released from all cells and accumulate into body fluids. They contain various proteins, lipids, nucleic acids (miRNA, mRNA, and DNA) and metabolites. In cancer, EV biomolecular composition and concentration are changed. Tumor EVs can promote the remodeling of the tumor microenvironment and pre-metastatic niche formation, and contribute to transfer of oncogenic potential or drug resistance during chemotherapy. This makes them a promising source of minimally invasive biomarkers. A limited number of clinical studies investigated EVs to monitor cancer progression, tumor evolution or drug resistance and several putative EV-bound protein and RNA biomarkers were identified. This review is focused on EVs as novel biomarker source for personalized medicine and pharmacogenomics in oncology. As several pharmacogenes and genes associated with targeted therapy, chemotherapy or hormonal therapy were already detected in EVs, they might be used for fine-tuning personalized cancer treatment.

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“…Moreover, these BCR-ABL1-positive exosomes were shown to be useful in determining the molecular remission grade. Future studies are needed to demonstrate if they are better or worse than conventional approaches at predicting CML relapse [130].…”

Section: Small-ev Cargo As Disease Markersmentioning

confidence: 99%

Exosomes and Extracellular Vesicles in Myeloid Neoplasia: The Multiple and Complex Roles Played by These “Magic Bullets”

Bernardi

Farina

2021

Biology

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Extracellular vesicles (exosomes, in particular) are essential in multicellular organisms because they mediate cell-to-cell communication via the transfer of secreted molecules. They are able to shuttle different cargo, from nucleic acids to proteins. The role of exosomes has been widely investigated in solid tumors, which gave us surprising results about their potential involvement in pathogenesis and created an opening for liquid biopsies. Less is known about exosomes in oncohematology, particularly concerning the malignancies deriving from myeloid lineage. In this review, we aim to present an overview of immunomodulation and the microenvironment alteration mediated by exosomes released by malicious myeloid cells. Afterwards, we review the studies reporting the use of exosomes as disease biomarkers and their influence in response to treatment, together with the recent experiences that have focused on the use of exosomes as therapeutic tools. The further development of new technologies and the increased knowledge of biological (exosomes) and clinical (myeloid neoplasia) aspects are expected to change the future approaches to these malignancies.

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Basic Knowledge on Bcr-Abl1-Positive Extracellular Vesicles

Cited by 8 publications

References 57 publications

Immunosuppressive Cell Subsets and Factors in Myeloid Leukemias

Immunosuppressive Cell Subsets and Factors in Myeloid Leukemias

Extracellular Vesicles: A Novel Tool Facilitating Personalized Medicine and Pharmacogenomics in Oncology

Exosomes and Extracellular Vesicles in Myeloid Neoplasia: The Multiple and Complex Roles Played by These “Magic Bullets”

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