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

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 CD71high/CD45-/Hoechsthigh 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.

New inflammatory indicators for cell-based liquid biopsy: association of the circulating CD44+/CD24− non-hematopoietic rare cell phenotype with breast cancer residual disease

“…The results may allow us to exclude circulating erythroblasts (CEB). CEB are represented by the CD71+/CD44±/24−/45− phenotype and are common in healthy and more so in afflicted individuals (Schreier, et al 2021b ). Findings of CD44+ CEB would allude to egress of earliest erythroblasts from the bone marrow as such allude to dysfunctional erythropoiesis (Schreier, et al 2021b ).…”

“…CEB are represented by the CD71+/CD44±/24−/45− phenotype and are common in healthy and more so in afflicted individuals (Schreier, et al 2021b ). Findings of CD44+ CEB would allude to egress of earliest erythroblasts from the bone marrow as such allude to dysfunctional erythropoiesis (Schreier, et al 2021b ). The review of in total 54 CD44+ CRC that were co-stained according to the CD71+/CD44±/24−/45− phenotype and derived from CD44+rich samples Nr.…”

“…Awareness is growing about some of those inflammation-associated non-hematopoietic cell types to circulate in the blood stream as a consequence of recruitment presumably from the bone marrow or as a consequence of detachment from a tissue lesion (Lin et al 2021 ; George et al 2004 ; Schreier and Triampo 2020 , 2021a ). More recently, our group intended to introduce the circulating erythroblast and their aberrations to represent bone marrow damage aimed at the assessment of systemic cancer (Schreier et al 2021b ). Such inflammation-associated circulating rare cell types represent valuable diagnostically exploitable abnormality that may persist as residual cancer disease and could be denoted as the circulating rare cell cancer inflammasome.…”

“…Alternatively, a spectrum of non-hematopoietic cell types are known to play role in chronic inflammatory processes and include parenchymal (Puré and Cuff 2001;Burger and Touyz 2012), endothelial (Lin et al 2021;Hida and Klagsbrun 2005;Bhakdi, et al 2019), stromal (Galland and Stamenkovic 2020) or mesothelial cells (Yung and Chan 2009). Awareness is growing about some of those inflammation-associated non-hematopoietic cell types to circulate in the blood stream as a consequence of recruitment presumably from the bone marrow or as a consequence of detachment from a tissue lesion (Lin et al 2021;George et al 2004;Schreier andTriampo 2020, 2021a). More recently, our group intended to introduce the circulating erythroblast and their aberrations to represent bone marrow damage aimed at the assessment of systemic cancer (Schreier et al 2021b).…”

Cancer-associated Systemic Abnormality: A Novel Marker Panel for Early-stage Breast Cancer Characterization

“…Further advancement in the field may be achieved by deeper investigations into the cancer-specific circulating rare cell population [12,13] what we would like to refer to as cancer-associated chronic systemic abnormality (CASA). Similar to CTC, CASA denotes blood circulating entities that however, are investigated in comprehension and include systemic representatives of localizable tumor growth, such as tumor-derived CTC, and tumor-associated circulating endothelial cells (CEC) [13][14][15][16]20] but also of non-localizable cancer that may include cancer inflammation-related cell types [22], CTC of unknown origin [16,19] and circulating erythroblasts (CEB) [21]. In awareness of the systemic and localizable nature of circulating rare cells, the idea prevailed to assess cancer burden in its entirety based on comprehensive circulating rare cells read-out [18] which would be potentially useful in monitoring response to interventions (in particular post-surgery interventions), to survey the chronic systemic cancer disease during therapy and in follow up as well as to predict recurrence at the earliest time point possible.…”