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. 1985 Feb;75(2):596–603. doi: 10.1172/JCI111736

Origin of cell populations after bone marrow transplantation. Analysis using DNA sequence polymorphisms.

D Ginsburg, J H Antin, B R Smith, S H Orkin, J M Rappeport
PMCID: PMC423535  PMID: 3882761

Abstract

After successful bone marrow transplantation, patient hematopoietic and lymphoid cells are replaced by cells derived from the donor marrow. To document and characterize successful engraftment, host and donor cells must be distinguished from each other. We have used DNA sequence polymorphism analysis to determine reliably the host or donor origin of posttransplant cell populations. Using a selected panel of six cloned DNA probes and associated sequence polymorphisms, at least one marker capable of distinguishing between a patient and his sibling donor can be detected in over 95% of cases. Posttransplant patient peripheral leukocytes were examined by DNA restriction enzyme digestion and blot hybridization analysis. We have studied 18 patients at times varying from 13 to 1,365 d after marrow transplantation. Mixed lymphohematopoietic chimerism was detected in 3 patients, with full engraftment documented in 15. One patient with severe combined immunodeficiency syndrome was demonstrated to have T cells of purely donor origin, with granulocytes and B cells remaining of host origin. Posttransplant leukemic relapse was studied in one patient and shown to be of host origin. DNA analysis was of particular clinical value in three cases where failure of engraftment or graft loss was suspected. In two of the three cases, full engraftment was demonstrated and in the third mixed lymphohematopoietic chimerism was detected. DNA sequence polymorphism analysis provides a powerful tool for the documentation of engraftment after bone marrow transplantation, for the evaluation of posttransplant lymphoma or leukemic relapse, and for the comprehensive study of mixed hematopoietic and lymphoid chimeric states.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Antonarakis S. E., Boehm C. D., Giardina P. J., Kazazian H. H., Jr Nonrandom association of polymorphic restriction sites in the beta-globin gene cluster. Proc Natl Acad Sci U S A. 1982 Jan;79(1):137–141. doi: 10.1073/pnas.79.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bell G. I., Karam J. H., Rutter W. J. Polymorphic DNA region adjacent to the 5' end of the human insulin gene. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5759–5763. doi: 10.1073/pnas.78.9.5759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blume K. G., Beutler E., Bross K. J., Schmidt G. M., Spruce W. E., Teplitz R. L. Genetic markers in human bone marrow transplantation. Am J Hum Genet. 1980 May;32(3):414–419. [PMC free article] [PubMed] [Google Scholar]
  4. Boehm C. D., Antonarakis S. E., Phillips J. A., 3rd, Stetten G., Kazazian H. H., Jr Prenatal diagnosis using DNA polymorphisms. Report on 95 pregnancies at risk for sickle-cell disease or beta-thalassemia. N Engl J Med. 1983 May 5;308(18):1054–1058. doi: 10.1056/NEJM198305053081803. [DOI] [PubMed] [Google Scholar]
  5. Borgaonkar D. S., Bias W. B., Sroka B. M., Hutchinson J. R., Santos G. W. Identification of graft and host cells in bone marrow transplants by the quinacrine banding technique of chromosome identification. Acta Cytol. 1974 May-Jun;18(3):263–267. [PubMed] [Google Scholar]
  6. Boyd C. N., Ramberg R. C., Thomas E. D. The incidence of recurrence of leukemia in donor cells after allogeneic bone marrow transplantation. Leuk Res. 1982;6(6):833–837. doi: 10.1016/0145-2126(82)90067-4. [DOI] [PubMed] [Google Scholar]
  7. Branch D. R., Gallagher M. T., Forman S. J., Winkler K. J., Petz L. D., Blume K. G. Endogenous stem cell repopulation resulting in mixed hematopoietic chimerism following total body irradiation and marrow transplantation for acute leukemia. Transplantation. 1982 Oct;34(4):226–228. doi: 10.1097/00007890-198210000-00018. [DOI] [PubMed] [Google Scholar]
  8. Cleary M. L., Chao J., Warnke R., Sklar J. Immunoglobulin gene rearrangement as a diagnostic criterion of B-cell lymphoma. Proc Natl Acad Sci U S A. 1984 Jan;81(2):593–597. doi: 10.1073/pnas.81.2.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gale R. P., Sparkes R. S., Golde D. W. Bone marrow origin of hepatic macrophages (Kupffer cells) in humans. Science. 1978 Sep 8;201(4359):937–938. doi: 10.1126/science.356266. [DOI] [PubMed] [Google Scholar]
  10. Grossbard E. B., Garrett T. J., Ratner L., Good R. A., O'Reilly R. J., Chaganti R. S. Alteration in lymphoid chimerism associated with cytomegalovirus infection after bone marrow transplantation. Transplantation. 1979 Sep;28(3):253–256. [PubMed] [Google Scholar]
  11. Hows J. M., Palmer S., Gordon-Smith E. C. Use of cyclosporin A in allogeneic bone marrow transplantation for severe aplastic anemia. Transplantation. 1982 Apr;33(4):382–386. doi: 10.1097/00007890-198204000-00008. [DOI] [PubMed] [Google Scholar]
  12. Hutz M. H., Michelson A. M., Antonarakis S. E., Orkin S. H., Kazazian H. H., Jr Restriction site polymorphism in the phosphoglycerate kinase gene on the X chromosome. Hum Genet. 1984;66(2-3):217–219. doi: 10.1007/BF00286604. [DOI] [PubMed] [Google Scholar]
  13. Kan Y. W., Lee K. Y., Furbetta M., Angius A., Cao A. Polymorphism of DNA sequence in the beta-globin gene region. Application to prenatal diagnosis of beta 0 thalassemia in Sardinia. N Engl J Med. 1980 Jan 24;302(4):185–188. doi: 10.1056/NEJM198001243020401. [DOI] [PubMed] [Google Scholar]
  14. Keating A., Singer J. W., Killen P. D., Striker G. E., Salo A. C., Sanders J., Thomas E. D., Thorning D., Fialkow P. J. Donor origin of the in vitro haematopoietic microenvironment after marrow transplantation in man. Nature. 1982 Jul 15;298(5871):280–283. doi: 10.1038/298280a0. [DOI] [PubMed] [Google Scholar]
  15. Miller G., Lipman M. Release of infectious Epstein-Barr virus by transformed marmoset leukocytes. Proc Natl Acad Sci U S A. 1973 Jan;70(1):190–194. doi: 10.1073/pnas.70.1.190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Orkin S. H., Alter B. P., Altay C., Mahoney M. J., Lazarus H., Hobbins J. C., Nathan D. G. Application of endonuclease mapping to the analysis and prenatal diagnosis of thalassemias caused by globin-gene deletion. N Engl J Med. 1978 Jul 27;299(4):166–172. doi: 10.1056/NEJM197807272990403. [DOI] [PubMed] [Google Scholar]
  17. Orkin S. H., Antonarakis S. E., Kazazian H. H., Jr Polymorphism and molecular pathology of the human beta-globin gene. Prog Hematol. 1983;13:49–73. [PubMed] [Google Scholar]
  18. Page D., de Martinville B., Barker D., Wyman A., White R., Francke U., Botstein D. Single-copy sequence hybridizes to polymorphic and homologous loci on human X and Y chromosomes. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5352–5356. doi: 10.1073/pnas.79.17.5352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Parkman R., Rappeport J., Camitta B., Levey R. H., Nathan D. G. Successful use of multiagent immunosuppression in the bone marrow transplantation of sensitized patients. Blood. 1978 Dec;52(6):1163–1169. [PubMed] [Google Scholar]
  20. Parkman R., Rappeport J., Geha R., Belli J., Cassady R., Levey R., Nathan D. G., Rosen F. S. Complete correction of the Wiskott-Aldrich syndrome by allogeneic bone-marrow transplantation. N Engl J Med. 1978 Apr 27;298(17):921–927. doi: 10.1056/NEJM197804272981701. [DOI] [PubMed] [Google Scholar]
  21. Prochownik E. V., Antonarakis S., Bauer K. A., Rosenberg R. D., Fearon E. R., Orkin S. H. Molecular heterogeneity of inherited antithrombin III deficiency. N Engl J Med. 1983 Jun 30;308(26):1549–1552. doi: 10.1056/NEJM198306303082601. [DOI] [PubMed] [Google Scholar]
  22. Rappeport J. M., Smith B. R., Parkman R., Rosen F. S. Application of bone marrow transplantation in genetic diseases. Clin Haematol. 1983 Oct;12(3):755–773. doi: 10.1016/s0308-2261(83)80009-5. [DOI] [PubMed] [Google Scholar]
  23. Reinherz E. L., Geha R., Rappeport J. M., Wilson M., Penta A. C., Hussey R. E., Fitzgerald K. A., Daley J. F., Levine H., Rosen F. S. Reconstitution after transplantation with T-lymphocyte-depleted HLA haplotype-mismatched bone marrow for severe combined immunodeficiency. Proc Natl Acad Sci U S A. 1982 Oct;79(19):6047–6051. doi: 10.1073/pnas.79.19.6047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schubach W. H., Hackman R., Neiman P. E., Miller G., Thomas E. D. A monoclonal immunoblastic sarcoma in donor cells bearing Epstein-Barr virus genomes following allogeneic marrow grafting for acute lymphoblastic leukemia. Blood. 1982 Jul;60(1):180–187. [PubMed] [Google Scholar]
  25. Singer J. W., Keating A., Ramberg R., McGuffin R., Sanders J. E., Sale G., Fialkow P. J., Thomas E. D. Long-term stable hematopoietic chimerism following marrow transplantation for acute lymphoblastic leukemia: a case report with in vitro marrow culture studies. Blood. 1983 Oct;62(4):869–872. [PubMed] [Google Scholar]
  26. Smith C. I., Aarli J. A., Biberfeld P., Bolme P., Christensson B., Gahrton G., Hammarström L., Lefvert A. K., Lönnqvist B., Matell G. Myasthenia gravis after bone-marrow transplantation. Evidence for a donor origin. N Engl J Med. 1983 Dec 22;309(25):1565–1568. doi: 10.1056/NEJM198312223092508. [DOI] [PubMed] [Google Scholar]
  27. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  28. Sparkes M. C., Crist M. L., Sparkes R. S., Gale R. P., Feig S. A. Gene markers in human bone marrow transplantation. Vox Sang. 1977 Oct;33(4):202–205. doi: 10.1111/j.1423-0410.1977.tb04464.x. [DOI] [PubMed] [Google Scholar]
  29. Thomas E. D., Buckner C. D., Sanders J. E., Papayannopoulou T., Borgna-Pignatti C., De Stefano P., Sullivan K. M., Clift R. A., Storb R. Marrow transplantation for thalassaemia. Lancet. 1982 Jul 31;2(8292):227–229. doi: 10.1016/s0140-6736(82)90319-1. [DOI] [PubMed] [Google Scholar]
  30. Thomas E. D., Ramberg R. E., Sale G. E., Sparkes R. S., Golde D. W. Direct evidence for a bone marrow origin of the alveolar macrophage in man. Science. 1976 Jun 4;192(4243):1016–1018. doi: 10.1126/science.775638. [DOI] [PubMed] [Google Scholar]
  31. Witherspoon R. P., Schanfield M. S., Storb R., Thomas E. D., Giblett E. R. Immunoglobulin production of donor origin after marrow transplantation for acute leukemia or aplastic anemia. Transplantation. 1978 Dec;26(6):407–408. doi: 10.1097/00007890-197812000-00008. [DOI] [PubMed] [Google Scholar]
  32. Wyman A. R., White R. A highly polymorphic locus in human DNA. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6754–6758. doi: 10.1073/pnas.77.11.6754. [DOI] [PMC free article] [PubMed] [Google Scholar]

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