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      Circulating erythroblast abnormality associated with systemic pathologies may indicate bone marrow damage

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          ABSTRACT

          Background:

          The circulating rare cell population is diverse and rich in diagnostic information. Its characterization and clinical exploitation by cell-based liquid biopsy is an ongoing research task. Bone marrow is one of the major contributors to the peripheral blood rare cell population and, consequently, determines individual rare cell profiles thus depending on bone marrow health status. Bone marrow damage has been associated with aggressive or late-stage systemic diseases and egress of various bone marrow cells into the blood circulation. The association of quantity and heterogeneity of circulating erythroblast with bone marrow damage is of particular interest.

          Methods:

          Circulating CD71 high/CD45-/Hoechst high blast cells from healthy, noncancer- and cancer-afflicted donors were enriched by CD45 depletion and analyzed by immunofluorescence microscopy.

          Results:

          A new finding of aberrant and mitotic circulating erythroid-like cells that appear similar across blood donors afflicted with various systemic pathologies is reported. Further presented is a classification of said erythroblast-like cells in nine subcategories according to morphological differences between phenotypically similar cells.

          Conclusion:

          Aberrant and mitotic bone marrow-derived rare circulating erythroid-like cells can be detected in the blood of afflicted individuals but not in healthy donors, suggesting the cause of bone marrow damage.

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          Most cited references32

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          Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases.

          The purpose of this study was to determine the accuracy, precision, and linearity of the CellSearch system and evaluate the number of circulating tumor cells (CTCs) per 7.5 mL of blood in healthy subjects, patients with nonmalignant diseases, and patients with a variety of metastatic carcinomas. The CellSearch system was used to enumerate CTCs in 7.5 mL of blood. Blood samples spiked with cells from tumor cell lines were used to establish analytical accuracy, reproducibility, and linearity. Prevalence of CTCs was determined in blood from 199 patients with nonmalignant diseases, 964 patients with metastatic carcinomas, and 145 healthy donors. Enumeration of spiked tumor cells was linear over the range of 5 to 1,142 cells, with an average recovery of >/=85% at each spike level. Only 1 of the 344 (0.3%) healthy and nonmalignant disease subjects had >/=2 CTCs per 7.5 mL of blood. In 2,183 blood samples from 964 metastatic carcinoma patients, CTCs ranged from 0 to 23,618 CTCs per 7.5 mL (mean, 60 +/- 693 CTCs per 7.5 mL), and 36% (781 of 2,183) of the specimens had >/=2 CTCs. Detection of >/=2 CTCs occurred at the following rates: 57% (107 of 188) of prostate cancers, 37% (489 of 1,316) of breast cancers, 37% (20 of 53) of ovarian cancers, 30% (99 of 333) of colorectal cancers, 20% (34 of 168) of lung cancers, and 26% (32 of 125) of other cancers. The CellSearch system can be standardized across multiple laboratories and may be used to determine the clinical utility of CTCs. CTCs are extremely rare in healthy subjects and patients with nonmalignant diseases but present in various metastatic carcinomas with a wide range of frequencies.
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            Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy.

            "Liquid biopsy" focusing on the analysis of circulating tumor cells (CTC) and circulating cell-free tumor DNA (ctDNA) in the blood of patients with cancer has received enormous attention because of its obvious clinical implications for personalized medicine. Analyses of CTCs and ctDNA have paved new diagnostic avenues and are, to date, the cornerstones of liquid biopsy diagnostics. The present review focuses on key areas of clinical applications of CTCs and ctDNA, including detection of cancer, prediction of prognosis in patients with curable disease, monitoring systemic therapies, and stratification of patients based on the detection of therapeutic targets or resistance mechanisms.
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              American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer.

              To update the recommendations for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of breast cancer. For the 2007 update, an Update Committee composed of members from the full Panel was formed to complete the review and analysis of data published since 1999. Computerized literature searches of MEDLINE and the Cochrane Collaboration Library were performed. The Update Committee's literature review focused attention on available systematic reviews and meta-analyses of published tumor marker studies. In general, significant health outcomes (overall survival, disease-free survival, quality of life, lesser toxicity, and cost-effectiveness) were used for making recommendations. Recommendations and Thirteen categories of breast tumor markers were considered, six of which were new for the guideline. The following categories showed evidence of clinical utility and were recommended for use in practice: CA 15-3, CA 27.29, carcinoembryonic antigen, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, urokinase plasminogen activator, plasminogen activator inhibitor 1, and certain multiparameter gene expression assays. Not all applications for these markers were supported, however. The following categories demonstrated insufficient evidence to support routine use in clinical practice: DNA/ploidy by flow cytometry, p53, cathepsin D, cyclin E, proteomics, certain multiparameter assays, detection of bone marrow micrometastases, and circulating tumor cells.
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                Author and article information

                Journal
                J Circ Biomark
                J Circ Biomark
                JCB
                Journal of Circulating Biomarkers
                AboutScience
                1849-4544
                31 August 2021
                Jan-Dec 2021
                : 10 ,2021
                : 14-19
                Affiliations
                [1 ] School of Bioinnovation and Bio-based Product Intelligence, Faculty of Science, Mahidol University, Rama VI Rd, Bangkok - Thailand
                [2 ] Thailand Center of Excellence in Physics, Ministry of Higher Education, Science, Research and Innovation, Bangkok - Thailand
                [3 ] Premise Biosystems Co., Ltd. Bangkok - Thailand
                [4 ] Excellent Center for Drug Discovery, Faculty of Science, Mahidol University, Rama VI, Rd, Bangkok - Thailand
                [5 ] Department of Oncology, Bangkok Hospital, Bangkok - Thailand
                [6 ] Department of Physics, Faculty of Science, Mahidol University, Bangkok - Thailand
                Author notes
                Corresponding author:School of Bioinnovation and Bio-based Product Intelligence Faculty of ScienceMahidol UniversityRama VI Rd, Bangkok 10400 - Thailandstefan.scr@mahidol.edu
                Article
                10.33393/jcb.2021.2220
                8493595
                b0455a28-6c9b-496a-944f-c6460ab20aff
                Copyright © 2021, The Authors

                Journal of Circulating Biomarkers - ISSN 1849-4544 - www.aboutscience.eu/jcb

                © 2021 The Authors. This article is published by AboutScience and licensed under Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Commercial use is not permitted and is subject to Publisher’s permissions. Full information is available at www.aboutscience.eu

                History
                : 7 December 2020
                : 14 July 2021
                Categories
                Short Communication

                bone cancer,bone marrow damage,circulating rare cells,erythroblast,liquid biopsy

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