Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

CD34+ Cells

Persistent decrease in proliferative potential of marrow CD34+cells exposed to early-acting growth factors after autologous bone marrow transplantation

Bone Marrow Transplantation volume 29, pages 557–562 (2002)Cite this article

Abstract

Post-graft hematopoiesis is characterized by long-term quantitative deficiency in marrow progenitor cells in both autologous and allogenic settings. In order to evaluate the function of post-graft progenitor cells, the proliferative capacity of marrow CD34+ cells was evaluated in 10 patients 6 months after autologous bone marrow transplantation (ABMT) for non-Hodgkin's lymphoma and compared to that of 10 patients before ABMT and 10 normal controls. Immuno-selected CD34+ cells were cultured for 7 days in liquid serum-free medium with a combination of early-acting GF consisting of stem cell factor, IL-3 and IL-1β. Clonogenic efficiency of unselected cells for CFU-GM and BFU-E was decreased in post-graft patients compared to pre-graft and control patients. However, clonogenic efficiency of selected CD34+ cells for CFU-GM was not different in post-graft, pre-graft and control patients but BFU-E values of post-graft patients remained lower than those of control patients. Decreased percentages of CD34+ CD38− cells were observed in both post-graft and pre-graft patients while those of CD34+ c-kit+ cells were similar in all three patient groups. After 7-day liquid culture, expansion yields of total progenitor cells were significantly lower in post-graft patients (147 ± 28%) than in pre-graft (255 ± 27%) and control patients (246 ± 23%). Post-graft deficiency in progenitor cell expansion was particularly marked for BFU-E (61 ± 24%) compared to pre-graft patients (220 ± 82%) and to controls (349 ± 82%). These results indicate impaired proliferative potential of marrow CD34+ cells several months after ABMT involving erythroid progenitor cells and/or commitment towards erythroid lineage from a more immature stage (pre-CFU).

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Szilvassy SJ, Fraser CC, Eaves CJ et al. Retrovirus-mediated gene transfer to purified hemopoietic stem cells with long-term lympho-myelopoietic repopulating ability Proc Natl Acad Sci USA 1989 86: 8798 8802

    Article  CAS  Google Scholar 

  2. Wolf NS, Kone A, Priestley GV, Bartelmez SH . In vivo and in vitro characterization of long-term repopulating primitive hematopoietic cells isolated by sequential Hoechst 33342–rhodamine 123 FACS selection Exp Hematol 1993 21: 614 622

    CAS  PubMed  Google Scholar 

  3. Messner HA, Curtis JE, Minden MD et al. Clonogenic hemopoietic precursors in bone marrow transplantation Blood 1987 70: 1425 1432

    CAS  PubMed  Google Scholar 

  4. Domenech J, Linassier C, Gihana E et al. Prolonged impairment of hematopoiesis after high-dose therapy followed by autologous bone marrow transplantation Blood 1995 85: 3320 3327

    CAS  Google Scholar 

  5. Darrington DL, Vose JM, Anderson JR et al. Incidence and characterization of secondary myelodysplastic syndrome and acute myelogenous leukemia following high-dose chemoradiotherapy and autologous stem-cell transplantation for lymphoid malignancies J Clin Oncol 1994 12: 2527 2534

    Article  CAS  Google Scholar 

  6. Friedberg JW, Neuberg D, Stone RM et al. Outcome in patients with myelodysplastic syndrome after autologous bone marrow transplantation for non-Hodgkin's lymphoma J Clin Oncol 1999 17: 3128 3135

    Article  CAS  Google Scholar 

  7. Miller JS, Arthur DC, Litz CE et al. Myelodysplastic syndrome after autologous bone marrow transplantation: an additional late complication of curative cancer therapy (see comments) Blood 1994 83: 3780 3786

    CAS  Google Scholar 

  8. Stone RM, Neuberg D, Soiffer R et al. Myelodysplastic syndrome as a late complication following autologous bone marrow transplantation for non-Hodgkin's lymphoma J Clin Oncol 1994 12: 2535 2542

    Article  CAS  Google Scholar 

  9. Herault O, Binet C, Degenne M et al. In vitro effect of stem cell factor on human clonogenic marrow progenitors after myeloablative treatments Eur J Haematol 1998 61: 113 118

    Article  CAS  Google Scholar 

  10. Dexter TM, Allen TD, Lajtha LG . Conditions controlling the proliferation of haemopoietic stem cells in vitro J Cell Physiol 1977 91: 335 344

    Article  CAS  Google Scholar 

  11. Domenech J, Gihana E, Dayan A et al. Haemopoiesis of transplanted patients with autologous marrows assessed by long-term marrow culture Br J Haematol 1994 88: 488 496

    Article  CAS  Google Scholar 

  12. Cartron G, Herault O, Benboubker L et al. Quantitative and qualitative analysis of the human primitive progenitor cell compartment after autologous stem cell transplantation J Hematother Stem Cell Res 2002 (in press)

  13. Lebkowski JS, Schain LR, Okrongly D et al. Rapid isolation of human CD34 hematopoietic stem cells – purging of human tumor cells Transplantation 1992 53: 1011 1019

    Article  CAS  Google Scholar 

  14. Haas R, Witt B, Mohle R et al. Sustained long-term hematopoiesis after myeloablative therapy with peripheral blood progenitor cell support Blood 1995 85: 3754 3761

    CAS  Google Scholar 

  15. Novitzky N, Mohammed R . Alterations in the progenitor cell population follow recovery from myeloablative therapy and bone marrow transplantation Exp Hematol 1997 25: 471 477

    CAS  PubMed  Google Scholar 

  16. Rusten LS, Jacobsen SE, Kaalhus O et al. Functional differences between CD38− and DR− subfractions of CD34+ bone marrow cells Blood 1994 84: 1473 1481

    CAS  PubMed  Google Scholar 

  17. Terstappen LW, Huang S, Safford M et al. Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38− progenitor cells Blood 1991 77: 1218 1227

    CAS  Google Scholar 

  18. Neben S, Hellman S . Montgomery M et al. Hematopoietic stem cell deficit of transplanted bone marrow previously exposed to cytotoxic agents Exp Hematol 1993 21: 156 162

    CAS  Google Scholar 

  19. Robinson SN, Freedman AS, Neuberg DS et al. Loss of marrow reserve from dose-intensified chemotherapy results in impaired hematopoietic reconstitution after autologous transplantation: CD34(+), CD34(+)38(−), and week-6 CAFC assays predict poor engraftment Exp Hematol 2000 28: 1325 1333

    Article  CAS  Google Scholar 

  20. Soligo DA, Lambertenghi Deliliers G, Servida F et al. Haematopoietic abnormalities after autologous stem cell transplantation in lymphoma patients Bone Marrow Transplant 1998 21: 15 22

    Article  CAS  Google Scholar 

  21. Voso MT, Murea S, Goldschmidt H et al. High-dose therapy with peripheral blood stem cell transplantation results in a significant reduction of the haemopoietic progenitor cell compartment Br J Haematol 1996 94: 759 766

    Article  CAS  Google Scholar 

  22. Podesta M, Piaggio G, Frassoni F et al. Deficient reconstitution of early progenitors after allogeneic bone marrow transplantation Bone Marrow Transplant 1997 19: 1011 1017

    Article  CAS  Google Scholar 

  23. Selleri C, Maciejewski JP, De Rosa G et al. Long-lasting decrease of marrow and circulating long-term culture initiating cells after allogeneic bone marrow transplant Bone Marrow Transplant 1999 23: 1029 1037

    Article  CAS  Google Scholar 

  24. Novitzky N, Mohamed R . Alterations in both the hematopoietic microenvironment and the progenitor cell population follow the recovery from myeloablative therapy and bone marrow transplantation Exp Hematol 1995 23: 1661 1666

    CAS  Google Scholar 

  25. Hellman S, Botnick LE, Hannon EC, Vigneulle RM . Proliferative capacity of murine hematopoietic stem cells Proc Natl Acad Sci USA 1978 75: 490 494

    Article  CAS  Google Scholar 

  26. Mauch P, Botnick LE, Hannon EC et al. Decline in bone marrow proliferative capacity as a function of age Blood 1982 60: 245 252

    CAS  PubMed  Google Scholar 

  27. Mauch P, Hellman S . Loss of hematopoietic stem cell self-renewal after bone marrow transplantation Blood 1989 74: 872 875

    CAS  Google Scholar 

  28. Lansdorp PM, Dragowska W, Mayani H . Ontogeny-related changes in proliferative potential of human hematopoietic cells J Exp Med 1993 178: 787 791

    Article  CAS  Google Scholar 

  29. Vaziri H, Dragowska W, Allsopp RC et al. Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age Proc Natl Acad Sci USA 1994 91: 9857 9860

    Article  CAS  Google Scholar 

  30. Wynn RF, Cross MA, Hatton C et al. Accelerated telomere shortening in young recipients of allogeneic bone-marrow transplants Lancet 1998 351: 178 181

    Article  CAS  Google Scholar 

  31. Akiyama M, Asai O, Kuraishi Y et al. Shortening of telomeres in recipients of both autologous and allogeneic hematopoietic stem cell transplantation Bone Marrow Transplant 2000 25: 441 447

    Article  CAS  Google Scholar 

  32. Domenech J, Roingeard F, Herault O et al. Changes in the functional capacity of marrow stromal cells after autologous bone marrow transplantation Leuk Lymphoma 1998 29: 533 546

    Article  CAS  Google Scholar 

  33. Roingeard F, Binet C, Lecron JC et al. Cytokines released in vitro by stromal cells from autologous bone marrow transplant patients with lymphoid malignancy Eur J Haematol 1998 61: 100 108

    Article  CAS  Google Scholar 

  34. Galotto M, Berisso G, Delfino L et al. Stromal damage as consequence of high-dose chemo/radiotherapy in bone marrow transplant recipients Exp Hematol 1999 27: 1460 1466

    Article  CAS  Google Scholar 

  35. Grande T, Bueren JA . Involvement of the bone marrow stroma in the residual hematopoietic damage induced by irradiation of adult and young mice Exp Hematol 1994 22: 1283 1287

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Professors M Marchand and M Aupart for kindly providing normal bone marrow samples. This study was supported by grants from the Ministère de la Recherche No. 995101061R1 and from Amgen-France.

Author information

Authors and Affiliations

  1. UPRES-EA 3249, Laboratory of Hematology, University Hospital of Tours, Tours, France

    J Domenech, G Cartron, N Clement, M-H Estienne, O Herault, D Truglio, F Roingeard & C Binet

  2. Department of Medical Oncology and Blood Diseases, UPRES-EA 3249, University Hospital of Tours, Tours, France

    G Cartron, L Benboubker & P Colombat

  3. UPRES-EA 3249, Regional Blood Bank, University Hospital of Tours, Tours, France

    I Desbois

Authors
  1. J Domenech
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G Cartron
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N Clement
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M-H Estienne
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. O Herault
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D Truglio
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L Benboubker
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. F Roingeard
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. I Desbois
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. P Colombat
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. C Binet
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Domenech, J., Cartron, G., Clement, N. et al. Persistent decrease in proliferative potential of marrow CD34+cells exposed to early-acting growth factors after autologous bone marrow transplantation. Bone Marrow Transplant 29, 557–562 (2002). https://doi.org/10.1038/sj.bmt.1703512

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703512

Keywords

This article is cited by

Search

Advanced search

Quick links