Lymphocyte Reproductive Activity Normalized to Numbers of Hematopoietic Stem Cells in Blood and Rate of Death in Fatal Diseases
International Journal of Genetics and Genomics
Volume 5, Issue 5, October 2017, Pages: 54-62
Received: Jan. 29, 2017; Accepted: Feb. 13, 2017; Published: Oct. 18, 2017
Views 3596      Downloads 200
Aleksei N. Shoutko, Laboratory for Improvement of the Treatment Methods, Federal Research Center for Radiology and Surgical Technologies, Saint-Petersburg, Russia
Olga A. Gerasimova, Transplantation Division, Federal Research Center for Radiology and Surgical Technologies, Saint-Petersburg, Russia
Ludmila P. Ekimova, Laboratory for Improvement of the Treatment Methods, Federal Research Center for Radiology and Surgical Technologies, Saint-Petersburg, Russia
Fiodor Zherebtsov, Transplantation Division, Federal Research Center for Radiology and Surgical Technologies, Saint-Petersburg, Russia
Viktor F. Mus, Group for Lung Cancer Treatment, Federal Research Center for Radiology and Surgical Technologies, Saint-Petersburg, Russia
Kirill S. Matyurin, Laboratory for Improvement of the Treatment Methods, Federal Research Center for Radiology and Surgical Technologies, Saint-Petersburg, Russia
Anatoly M. Granov, Transplantation Division, Federal Research Center for Radiology and Surgical Technologies, Saint-Petersburg, Russia
Article Tools
Follow on us
The numbers of CD133+ and CD31+ lymphocytes and those in the G2-M phases in the total fraction of circulating lymphocytes from patients with fatal liver cirrhosis and advanced lung cancer were investigated by flow cytometry during a long period of conventional treatment with OLT or palliative surgery followed by myelosuppressive chemotherapy. The relationships of specific reproductive activity, sRA (G2-M/CD133+), and the number of committed liver α-fetoprotein-positive (AFP+) cells with the rate of patient deaths, characterized by exponential approximation survival curves for both diseases, were investigated. Subnormal sRA in patients after OLT and excessive sRA in LC patients above a healthy level were associated with higher death rates and lower survival, coinciding with strong immunosuppression caused by anti-rejection and anti-cancer therapies. These findings may be explained by morphogenesis (feeding) activity of circulating lymphocytes targeted toward both normal and malignant tissues rather than in terms of cellular immunity. The sRA changes may be a useful indicator for monitoring the potential for engraftment or tumor growth.
Hematopoietic Stem Cells, Lymphocytes, Specific Reproductive Activity, Resource of Lymphopoiesis, Lung Cancer Therapy, Liver Transplantation, Death Rate
To cite this article
Aleksei N. Shoutko, Olga A. Gerasimova, Ludmila P. Ekimova, Fiodor Zherebtsov, Viktor F. Mus, Kirill S. Matyurin, Anatoly M. Granov, Lymphocyte Reproductive Activity Normalized to Numbers of Hematopoietic Stem Cells in Blood and Rate of Death in Fatal Diseases, International Journal of Genetics and Genomics. Vol. 5, No. 5, 2017, pp. 54-62. doi: 10.11648/j.ijgg.20170505.12
Copyright © 2017 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
M. Kucia, J. Ratajczak, and MZ. Ratajczak, Bone marrow as a source of circulating CXCR4+tissue- committed stem cells, Biol Cell, vol. 97 (2), pp. 133-146, February 2005. doi:10.1042/BC20040069.
Ch. Drapeau, Cracking the stem cell code: demystifying the most dramatic scientific breakthrough of our times. Hillsboro, Or, Goodwill Books USA, Sutton Hart Press/1st ed. 2010.
A. N. Shoutko, O. A. Gerasimova, L. P. Ekimova, F. K. Zherebtsov V. F. Mus, D. A. Granov, and A. M. Granov, Long -term activation of circulating liver-committed mononuclear cells after OLT, J J Regener Med, vol. 1 (3), pp.011, March 2016.
A. Shoutko, L. Ekimova, V. Mus, and V. Sokurenko, Fluctuations of CD34 cells number in blood of cancer patients during final year of life, Medical and Health Science Journal (MHSJ), 2012. vol.13 (4), pp.7-13, January 2012. doi:
B.-S. Ding, D. James, R. Iyer, I. Falciatori, D. Hambardzumyan, Su Wang, J. M. Butler, S. Y. Rabbany, and A.Hormigo, Prominin 1/CD133 endothelium sustains growth of proneural glioma, PloS ONE, vol. 8 (4), pp. e62150, April 2013. doi:10.1371/journal.pone.0062150.
I. Colmegna, A. Diaz-Borjon, H. Fujii, L. Schaefer, J. J. Goronzy, and C M. Weyand, Defective proliferative capacity and accelerated telomeric loss of hematopoietic progenitor cells in rheumatoid arthritis, Arthritis Rheum, vol. 58 (4),pp. 990-1000. April 2008. doi: 10.1002/art.23287.
G. Van Zant, and Ying Liang, Concise Review: Hematopoietic stem cell aging, life span, and transplantation, Stem Cells Transplantational Medicine, vol.1 (9), pp. 651–657, September 2012.doi:10 5966/sctm.2012-0033.
H. Silva, and I. M. Conboy, Aging and stem cell renewal, in: Stem Book,internet, L. Girard, Ed., Harvard Stem Cell Institute, Harvard University, July, 2008. PMID: 20614587: doi: 10.3824/stembook.1.11.1 doi/10.3824/stembook.1.11.1,
A. N. Shoutko, and L. P. Ekimova. The impact of middle age on the viability of patients with nonmalignant and malignant diseases. Cancer Research Journal, vol. 2 (6), pp. 114-120, December 2014. doi: 10.11648/j.crj.20140206.14 10.
L. Chen, Y. Lou, Y. Chen, and J. Yang, Prognostic value of the neutrophil-to-lymphocyte ratio inpatients with acute-on-chronic liver failure, Int J Clin Pract, 68 (8), pp. 1034–1040, August 2014. doi: 10.1111/ijcp.12408.
A. M. Granov, D. A. Granov, F. K. Zherebtsov, O. A. Gerasimova, V. V. Borovik, V. V. Osovskikh, D. N. Maystrenko, I. O. Rutkin, S. P. Tsurupa, I. I. Tileubergenov, S. V. Shapoval, and T. G. Mikhaylichenko, Livertransplantation. A single center experience of 100 cases, Vestnik transplantologii I iskusstvennich organov, vol. 14 (4), pp.11-16, December 2012›.
Curve fitting project -, pp. 1-4.
Sh. S. Eaker, T. S. Hawley, A. Ramezani, and R. G. Hawley, Detection and enrichment of hematopoietic stem cells by side population phenotype, in: Methods in molecular biology: flow cytometry protocols, 2nd ed., T. S. Hawley and R. G. Hawley Eds., © Humana Press Inc., Totowa, NJ, 2004, pp161-180.
I. Sales-Pardo, A. Avendaño, V. Martinez-Muñoz, M. García-Escarp, R. Celis, Ph. Whittle, J. Barquinero, J. C. Domingo, P. Marin, and J. Petriz, Flow cytometry of the side population: tips& tricks, Cellular oncology, vol. 28 (1-2), pp. 37–53, January 2006.
St. L. Nelson, Statistical formulas in Excel.
J. L. Loveland,. Mathematical justification of introductory hypothesis tests and development of reference Materials, (report for M. Sc. “Mathematics”). Utah State University, 2011, Retrieved April/2013.›...› GRADREPORTS› 14.
A. Medkhaly, E. Simoneau, S. Doi, P. Metrakos, and M. Hassanain, Developing a prognostic score for early prediction of graft and patient survival after orthotopic liver transplantation Am J Transplant, 2013; 13 (suppl 5).
Lee S-G, Hwang Sh, LeeY-J, Park K-M, Jeon H-B, Min PCh. Regeneration of graft liver in adult-to-adult living donor liver transplantation using a left lobe graft. J. Korean Med. Sci. vol. 13 (4), pp. 350–354, August 1998.
A. Jain, J. Reyes, R. Kashyap, S. F. Dodson, A. J. Demetris, K. Ruppert, K. Abu-Elmagd, W. Marsh, J. Madariaga, G. Mazariegos, D. Geller, C. A. Bonham, T. Gayowski, T. Cacciarelli, P. Fontes, T. E. Starzl, and J. J. Fung, Long-term survival after liver transplantation in 4,000 consecutive patients at single center, Ann Surg, vol. 232 (4), pp. 490–500 October 2000. PMC1421181.
A. Ekka-Zochar, Y. Zitser-Gurevich, M. Mandel, I. Weiss-Salz, S. Nir, E. Mor, N. Richard, H. Merhav, R. Bruck, and E. Simchen, Graft survival and its determinants: a 3 year national experience with liver transplantation in Israel. IMAJ, vol.8 (6), pp.400–405, Dec. 2006. PMID: 16833169.
Zhong Li, CD133: a stem cell biomarker and beyond, Exp Hematol Oncol, 2 (17) July 2013.doi: 10.1186/2162-3619-2-17.
P. G. Bertolino, W. D. Mc Caughan, and G. Bowen, Role of primary intrahepatic T-cell activation in the ‘liver tolerance effect’, Immunology and Cell Biology, vol.80, pp.4–92, October2002. doi:10.1046/j.0818-9641.2001.01048.x.
R. Turner, O. Lozoya, Y. Wang, V. Cardinale, E. Gaudio, G. Alpini, G. Mendel, E. Wauthier, C. Barbier, D. Alvaro, and L. M. Reid, Human hepatic stem cell and maturation liver lineage biology, Hepatology, vol. 53 (3), pp.1035-1045, March 2011. PMID: 21374667, doi: 10.1002/hep.24157.
Y. Haruna, K. Saito, S. Spaulding, M. A. Nalesnik, and M. A. Gerber, Identification of bipotential progenitor cells in human liver development, Hepatology, vol. 23 (3), pp. 476-481, March 1996. PMID: 8617427, doi: 10.1002/hep.510230312.
O. D. Liang, T. Korff, J. Eckhardt, J. Rifaat, N. Baal, F. Herr, K. T. Preissner, and M. Zygmunt, Oncodevelopmental alpha-fetoprotein acts as a selective proangiogenic factor on endothelial cell from the fetomaternal unit. J Clin Endocrinol Metab, vol.89 (3), pp. 1415-22, March 2004. doi:
S. Schwartzenberg, A. Mor, G. Luboshits, D. Planer, V. G. Deutsch, G. Keren, and J. Georgeet, Association between circulating early endothelial progenitors and CD4+CD25+regulatory T-cells: a possible cross-talk between immunity and angiogenesis? Am J Immunol, vol.1 (4), pp. 143–147, 2005.
M. Romano, F. De Francesco, G. Pirozzi, E. Gringeri, R. Boetto, M. Di Domenico, B. Zavan, G A. Ferraro, and U. Cillo, Expression of cancer stem cell biomarkers as a tool for a correct therapeutic approach to hepatocellular carcinoma, Oncoscience, vol. 2 (5) pp. 443-456, doi: 10.18632/oncoscience.163, PMC4468330.
J. Hur, H.-M. Yang, Ch.-H. Yoon, Ch.-S. Lee, K.-W. Park, J.-H. Kim, T.-Y. Kim, J.-Y. Kim, H.-J. Kang, I.-H. Chae, B.-H. Oh, Y.-B. Park, and H.-S. Kim, Identification of a novel role of T-cells in postnatal vasculogenesis, Circulation, vol.116 (15) pp. 1671–1682, October 2007. PDF
Wenbo Meng, Xun Li, Zhongtian Bai, Yan Li, Jinqiu Yuan, Tao Liu, Jun Yan, Wence Zhou, Kexiang Zhu, Hui Zhang, and Yumin Li, Silencing alpha-fetoprotein inhibits VEGF and MMP-2/9 production in human hepatocellular carcinoma cell. PLoS ONE, 9 (2), pp. e90660, February 2014.
E. Arias, United States Life Tables, 2006, in: National vital statistics reports from U.S. Department of health and human services centers for disease control and prevention, National center for health statistics, National vital Statistics System, vol. 58 (21), pp.1-40, June 2010.
K. Billups, J. Neal, and J. Salyer, Immunosuppressant-driven de novo malignant neoplasms after solid-organ transplant, Progress in Transplantation, vol. 25 (2), pp. 182-188, June 2015. doi:
Karynsa Cetin, David S Ettinger, Yong-jiang Hei, and C. D. O’Malley, Survival by histologic subtype in stage IV nonsmall cell lung cancer based on data from the Surveillance, Epidemiology and End Results, Program Clinical Epidemiology, vol. 3, pp.139–148, April 2011. DOI: 10.2147/CLEP.S17191.
32 J. Baba, S. Watanabe, Y. Saida, T. Tanaka, T. Miyabayash, J. Koshio, K. Ichikawa, K. Nozaki, T. Koya, K. Deguchi, C. Tan, S. Miura, H. Tanaka, J. Tanaka, H. Kagamu, H.Yoshizawa, K. Nakata, and I. Narita, Depletion of radio-resistant regulatory T cells enhances antitumor immunity during recovery from lymphocytopenia, Blood, vol.120 (12),pp.2417-2427 July 2012. PMID: 22806892 doi: 10.1182/blood-2012-02-411124.
U.S. Department of health and human services, National institute of health, National cancer Institute,”Blood/bone marrow,” in: Common terminology criteria for adverse events (CTCAE)/Version 3.0, AMGEN Oncology, p.4, August 2006.
K. S. Tewari, J. J. Java, T. A. Gatcliffe, M. A. Bookman, and B. J. Monk, Chemotherapy-induced neutropenia as a biomarker of survival in advanced ovarian carcinoma: an exploratory study of the gynecologic oncology group, Gynecol Oncol, vol.133 (3), pp.439-445. March 2014. doi: 10.1016/j.ygyno.2014.03.013.
Z. Su, Y.-P. Mao, P.-Y. Ou Yang, J. Tang, X.-W. Lan, and F.-Y. Xie, Leucopenia and treatment efficacy in advanced nasopharyngeal carcinoma, BMC Cancer, vol.15, pp. 429. May 2015. doi:10.1186/s12885-015-1442-3.
A. Shoutko, L. Yurkova, K. Borodulya, and L. Ekimova, Lymphocytopenia and cytotoxic therapy in patients with advanced ovarian cancer, Cancer Research J, 3 (3), pp. 47-51, May 2015. doi:10.11648/j.crj.20150303.11.
W. W. Pang, E. A. Price, D. Sahoo, I. Beerman, W. J. Maloney, D. J. Rossi, S. L. Schrier, and I. L. Weissman, Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age, PNAS USA, vol.108, pp.20012–20017, June 2011. doi: 10.1073/pnas.1116110108.
A. N. Shoutko, and L. P. Ekimova Lymphocytopenia can contribute in common benefit of cytotoxic therapy of cancer, "Inter-Medical", vol.3,pp. 5-13, 2014.
A. Shoutko, L. Yurkova, K. Borodulya, and L. Ekimova, Protracted half-body irradiation instead of chemotherapy: life span and lymphocytopenia in relapsed ovarian cancer, Int J of Tumor Therapy, 5 (1), pp.1-7, Feb 2016. doi: 10.5923/j.ijtt.20160501.01.
A. N. Shoutko, and L. P. Ekimova Abnormal tissue proliferation and life span variability in chronically irradiated dogs, Radiat Environ Biophys, vol.53 (1), pp.65-72, March 2014. PMID: 24310526: doi: 10.1007/s00411-013-0504-7.
A. D. Hayward, I. Nenko, and V. Lummaa, Early-life reproduction is associated with increased mortality risk but enhanced lifetime fitness in pre-industrial humans Proc. R. Soc. B: Biological Sciencesss, vol.282(1804), pp. 20143053. March 2015. doi: 10.1098/rspb.2014.3053;
WHO Recommendations for prevention and treatment of pre-eclampsia and eclampsia. Geneva: World Health Organization, Background 1, Bookshelf ID: NBK1405632011, National Center for Biotechnology Information, U.S. National Library of Medicine 8600 Rockville Pike, Bethesda MD, 20894 USA.
P, Luppi, R. W. Powers, V. Verma, L. Edmunds, D. Plymire, and C. A. Hubel, Maternal circulating CD34+VEGFR-2+ and CD133+ VEGFR-2+ progenitor cells increase during normal pregnancy but are reduced in women with preeclampsia, Reprod Sci, vol. 17 (7), pp. 643–652, July 2010. doi: 10.1177/1933719110366164,; PMC2893245.
Science Publishing Group
1 Rockefeller Plaza,
10th and 11th Floors,
New York, NY 10020
Tel: (001)347-983-5186