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

Stefan Schreier; Prapaphan Budchart; Suparerk Borwornpinyo; Wichit Arpornwirat; Wannapong Triampo

doi:10.33393/jcb.2021.2220

Authors

Stefan Schreier School of Bioinnovation and Bio-based Product Intelligence, Faculty of Science, Mahidol University, Rama VI Rd, Bangkok, Thailand Center of Excellence in Physics, Ministry of Higher Education, Science, Research and Innovation, Bangkok and Premise Biosystems Co., Ltd. Bangkok - Thailand
Prapaphan Budchart Premise Biosystems Co., Ltd. Bangkok - Thailand
Suparerk Borwornpinyo Premise Biosystems Co., Ltd. Bangkok and Excellent Center for Drug Discovery, Faculty of Science, Mahidol University, Rama VI, Rd, Bangkok - Thailand
Wichit Arpornwirat Department of Oncology, Bangkok Hospital, Bangkok - Thailand
Wannapong Triampo Thailand Center of Excellence in Physics, Ministry of Higher Education, Science, Research and Innovation, Bangkok and Department of Physics, Faculty of Science, Mahidol University, Bangkok - Thailand

DOI:

https://doi.org/10.33393/jcb.2021.2220

Keywords:

Bone cancer, Bone marrow damage, Circulating rare cells, Erythroblast, Liquid biopsy

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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References

Millner LM, Linder MW, Valdes R Jr. Circulating tumor cells: a review of present methods and the need to identify heterogeneous phenotypes. Ann Clin Lab Sci. 2013;43(3):295-304. PMID:23884225

Alix-Panabières C, Pantel K. Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer Discov. 2016;6(5):479-491. https://doi.org/10.1158/2159-8290.CD-15-1483 PMID:26969689 DOI: https://doi.org/10.1158/2159-8290.CD-15-1483

Allard WJ, Matera J, Miller MC, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004;10(20):6897-6904. https://doi.org/10.1158/1078-0432.CCR-04-0378 PMID:15501967 DOI: https://doi.org/10.1158/1078-0432.CCR-04-0378

Bhakdi SC, Suriyaphol P, Thaicharoen P, et al. Accuracy of tumour-associated circulating endothelial cells as a screening biomarker for clinically significant prostate cancer." Cancers. 2019;11:1064. https://doi.org/10.3390/cancers11081064 https://pubmed.ncbi.nlm.nih.gov/31357651/ DOI: https://doi.org/10.3390/cancers11081064

Jones ML, Siddiqui J, Pienta KJ, Getzenberg RH. Circulating fibroblast-like cells in men with metastatic prostate cancer. Prostate. 2013;73(2):176-181. https://doi.org/10.1002/pros.22553PMID:22718300 DOI: https://doi.org/10.1002/pros.22553

Schreier S, Wannapong T. The blood circulating are cell population. What is it and what is it good for? Cells. 2020;9(4):790. https://doi.org/10.3390/cells9040790 PMID https://pubmed.ncbi.nlm.nih.gov/32218149/ DOI: https://doi.org/10.3390/cells9040790

Fadini GP, Avogaro A. It is all in the blood: the multifaceted contribution of circulating progenitor cells in diabetic complications. Exp Diabetes Res. 2012;2012:742976. https://doi.org/10.1155/2012/742976 PMID:22548049 DOI: https://doi.org/10.1155/2012/742976

Schreier S, Borwornpinyo S, Udomsangpetch R, Triampo W. An update of circulating rare cell types in healthy adult peripheral blood: findings of immature erythroid precursors. Ann Transl Med. 2018;6(20):406. https://doi.org/10.21037/atm.2018.10.04 PMID:30498733 DOI: https://doi.org/10.21037/atm.2018.10.04

Bessis M. L’ilot erythroblastique. Unite functionelle de la moelle osseuse. Rev Hematol (Paris). 1958;13:8-11.

Spike BT, Macleod KF. Effects of hypoxia on heterotypic macrophage interactions. Cell Cycle. 2007;6(21):2620-2624. https://doi.org/10.4161/cc.6.21.4879 PMID:17873523 DOI: https://doi.org/10.4161/cc.6.21.4879

Kobayashi Y, Takamatsu R, Sato S, et al. Erythroblast appearance associated with natalizumab. Mult Scler Relat Disord. 2019;29:145-147. https://doi.org/10.1016/j.msard.2019.01.041 PMID:30711880 DOI: https://doi.org/10.1016/j.msard.2019.01.041

Du R, Lu KV, Petritsch C, et al. HIF1a induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell. 2008;13:206-220. DOI: https://doi.org/10.1016/j.ccr.2008.01.034

Sankaran VG, Orkin SH, Walkley CR. Rb intrinsically promotes erythropoiesis by coupling cell cycle exit with mitochondrial biogenesis. Genes Dev. 2008;22:463-475. DOI: https://doi.org/10.1101/gad.1627208

Downey H. The megaloblast-normoblast problem: a cytologic study. J Lab Clin Med. 1952;39(6):837-864. PMID:14938726

Goasguen JE, Bennett JM, Bain BJ, et al; The International Working Group on Morphology of MDS. Dyserythropoiesis in the diagnosis of the myelodysplastic syndromes and other myeloid neoplasms: problem areas. Br J Haematol. 2018;182(4):526-533. https://doi.org/10.1111/bjh.15435 PMID:29917221 DOI: https://doi.org/10.1111/bjh.15435

Brunning RD, Orazi A, Germing U et al. Myelodysplastic syndromes/neoplasms, overview. In: World health organization classification of tumours of haematopoietic and lymphoid tissues 2008.

Iolascon A, Heimpel H, Wahlin A, Tamary H. Congenital dyserythropoietic anemias: molecular insights and diagnostic approach. Blood. 2013;122(13):2162-2166. https://doi.org/10.1182/blood-2013-05-468223 PMID:23940284 DOI: https://doi.org/10.1182/blood-2013-05-468223

Jaffray JA, Mitchell WB, Gnanapragasam MN, et al. Erythroid transcription factor EKLF/KLF1 mutation causing congenital dyserythropoietic anemia type IV in a patient of Taiwanese origin: review of all reported cases and development of a clinical diagnostic paradigm. Blood Cells Mol Dis. 2013;51(2):71-75. https://doi.org/10.1016/j.bcmd.2013.02.006PMID:23522491 DOI: https://doi.org/10.1016/j.bcmd.2013.02.006

Zhao B, Liu H, Mei Y, et al. Disruption of erythroid nuclear opening and histone release in myelodysplastic syndromes. Cancer Med. 2019;8(3):1169-1174. https://doi.org/10.1002/cam4.1969 PMID:30701702 DOI: https://doi.org/10.1002/cam4.1969

Bright M, Cobb J, Evans B, Parry TE. Congenital dyserythropoietic anaemia with erythroblastic multinuclearity. J Clin Pathol. 1972;25(7):561-569. https://doi.org/10.1136/jcp.25.7.561 PMID:5070252 DOI: https://doi.org/10.1136/jcp.25.7.561

Pantel K, Cote RJ, Fodstad O. Detection and clinical importance of micrometastatic disease. J Natl Cancer Inst. 1999;91(13):1113-1124. https://doi.org/10.1093/jnci/91.13.1113PMID:10393719 DOI: https://doi.org/10.1093/jnci/91.13.1113

Klein CA, Blankenstein TJ, Schmidt-Kittler O, et al. Genetic heterogeneity of single disseminated tumour cells in minimal residual cancer. Lancet. 2002;360(9334):683-689. https://doi.org/10.1016/S0140-6736(02)09838-0 PMID:12241875 DOI: https://doi.org/10.1016/S0140-6736(02)09838-0

Tharp D, Nandana S. How prostate cancer cells use strategy instead of brute force to achieve metastasis. Cancers (Basel). 2019;11(12):1928. https://doi.org/10.3390/cancers11121928PMID:31817000 DOI: https://doi.org/10.3390/cancers11121928

Diel IJ, Kaufmann M, Goerner R, Costa SD, Kaul S, Bastert G. Detection of tumor cells in bone marrow of patients with primary breast cancer: a prognostic factor for distant metastasis. J Clin Oncol. 1992;10(10):1534-1539. https://doi.org/10.1200/JCO.1992.10.10.1534PMID:1403032 DOI: https://doi.org/10.1200/JCO.1992.10.10.1534

Walter VP, Taran FA, Wallwiener M, Brucker SY, Hartkopf AD . Abstract P1-01-16: Detection of disseminated tumor cells in DCIS patients impacts local recurrence. San Antonio Breast Cancer Symposium; December 5–9, 2017; San Antonio, Texas. Cancer Res. 2018. https://doi.org/10.1158/1538-7445.SABCS17-P1-01-16. DOI: https://doi.org/10.1158/1538-7445.SABCS17-P1-01-16

Banys M, Hahn M, Gruber I, et al. Detection and clinical relevance of hematogenous tumor cell dissemination in patients with ductal carcinoma in situ. Breast Cancer Res Treat. 2014;144(3):531-538. https://doi.org/10.1007/s10549-014-2898-6 PMID:24590774 DOI: https://doi.org/10.1007/s10549-014-2898-6

Cote RJ, Rosen PP, Lesser ML, Old LJ, Osborne MP. Prediction of early relapse in patients with operable breast cancer by detection of occult bone marrow micrometastases. J Clin Oncol. 1991;9(10):1749-1756. https://doi.org/10.1200/JCO.1991.9.10.1749 PMID:1919627 DOI: https://doi.org/10.1200/JCO.1991.9.10.1749

Mignot F, Loirat D, Dureau S, et al. Disseminated tumor cells predict efficacy of regional nodal irradiation in early stage breast cancer. Int J Radiat Oncol Biol Phys. 2019;103(2):389-396. DOI: https://doi.org/10.1016/j.ijrobp.2018.09.033

Braun S, Vogl FD, Naume B, et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med. 2005;353(8):793-802. https://doi.org/10.1056/NEJMoa050434PMID:16120859 DOI: https://doi.org/10.1056/NEJMoa050434

Stefanovic S, Diel I, Sinn P, et al. Disseminated tumor cells in the bone marrow of patients with operable primary breast cancer: prognostic impact in immunophenotypic subgroups and clinical implication for bisphosphonate treatment. Ann Surg Oncol. 2016;23(3):757-766. https://doi.org/10.1245/s10434-015-4895-3 PMID:26467455 DOI: https://doi.org/10.1245/s10434-015-4895-3

Harris L, Fritsche H, Mennel R, et al; American Society of Clinical Oncology. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25(33):5287-5312. https://doi.org/10.1200/JCO.2007.14.2364PMID:17954709 DOI: https://doi.org/10.1200/JCO.2007.14.2364

Banys-Paluchowski M, Hartkopf A, Meier-Stiegen F, Janni W, Solomayer EF, Fehm T. Circulating and disseminated tumour cells in breast carcinoma: Report from the Consensus Conference on Tumour Cell Dissemination during the 38th Annual Meeting of the German Society of Senology, Berlin, 14 June 2018. Geburtshilfe Frauenheilkd. 2019;79(2):177-183. https://doi.org/10.1055/a-0753-7331 PMID:30792547 DOI: https://doi.org/10.1055/a-0753-7331