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. 1996 Apr;49(2):M112–M117. doi: 10.1136/mp.49.2.m112

Detection of clonal immunoglobulin gene rearrangements in the peripheral blood progenitor cells of patients with multiple myeloma: the potential role of purging with CD34 positive selection

R G Owen 1,2,3,4, A P Haynes 1,2,3,4, P A Evans 1,2,3,4, R J Johnson 1,2,3,4, A C Rawstron 1,2,3,4, G McQuaker 1,2,3,4, G M Smith 1,2,3,4, M C Galvin 1,2,3,4, D L Barnard 1,2,3,4, N H Russell 1,2,3,4, J A Child 1,2,3,4, G J Morgan 1,2,3,4
PMCID: PMC408031  PMID: 16696051

Abstract

Aims—To determine the extent of clonal cell contamination of peripheral blood progenitor cell (PBPC) collections in patients with multiple myeloma (MM) and to assess the purging efficacy of CD34 positive selection.

Methods—PBPC collections from 29 patients with MM were analysed for the presence of clonal immunoglobulin heavy chain (IgH) gene rearrangements with a fluorescence based PCR technique. In addition, the PBPC from eight of the 29 patients were “purged” by selection of CD34 positive haematopoietic progenitors with an avidin-biotin immunoabsorption column (Ceprate). In each case the unmanipulated PBPC, CD34 positive and waste fractions were all assessed for the presence of clonal IgH rearrangements.

Results—Clonal IgH rearrangements (identical with those demonstrated in diagnostic bone marrow samples) were demonstrated in 10 (35%) of 29 cases and seemed to be confined to those with significant residual bone marrow disease. Clonal rearrangements were evident in the PBPC of two of the eight patients who underwent CD34 selection; in both instances a “clonal purge” was seen as it was not possible to demonstrate the clonal rearrangement in the CD34 positive fraction. In four of the six remaining cases the normal polyclonal fingerprint could not be demonstrated in the CD34 positive fraction, which is consistent with a significant reduction in contaminating B cells.

Conclusions—Clonal cells contaminate PBPC collections in a significant proportion of patients with MM and may be eliminated by CD34 positive selection.

Keywords: PCR

Keywords: myeloma

Keywords: CD34

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M112

Selected References

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

  1. Berenson J., Wong R., Kim K., Brown N., Lichtenstein A. Evidence for peripheral blood B lymphocyte but not T lymphocyte involvement in multiple myeloma. Blood. 1987 Nov;70(5):1550–1553. [PubMed] [Google Scholar]
  2. Billadeau D., Quam L., Thomas W., Kay N., Greipp P., Kyle R., Oken M. M., Van Ness B. Detection and quantitation of malignant cells in the peripheral blood of multiple myeloma patients. Blood. 1992 Oct 1;80(7):1818–1824. [PubMed] [Google Scholar]
  3. Bird J. M., Bloxham D., Samson D., Marcus R. E., Russell N. H., Kelsey S. M., Newland A. C., Apperley J. F. Molecular detection of clonally rearranged cells in peripheral blood progenitor cell harvests from multiple myeloma patients. Br J Haematol. 1994 Sep;88(1):110–116. doi: 10.1111/j.1365-2141.1994.tb04985.x. [DOI] [PubMed] [Google Scholar]
  4. Brenner M. K., Rill D. R., Moen R. C., Krance R. A., Mirro J., Jr, Anderson W. F., Ihle J. N. Gene-marking to trace origin of relapse after autologous bone-marrow transplantation. Lancet. 1993 Jan 9;341(8837):85–86. doi: 10.1016/0140-6736(93)92560-g. [DOI] [PubMed] [Google Scholar]
  5. Brugger W., Bross K. J., Glatt M., Weber F., Mertelsmann R., Kanz L. Mobilization of tumor cells and hematopoietic progenitor cells into peripheral blood of patients with solid tumors. Blood. 1994 Feb 1;83(3):636–640. [PubMed] [Google Scholar]
  6. Chiu E. K., Ganeshaguru K., Hoffbrand A. V., Mehta A. B. Circulating monoclonal B lymphocytes in multiple myeloma. Br J Haematol. 1989 May;72(1):28–31. doi: 10.1111/j.1365-2141.1989.tb07646.x. [DOI] [PubMed] [Google Scholar]
  7. Corradini P., Voena C., Omedé P., Astolfi M., Boccadoro M., Dalla-Favera R., Pileri A. Detection of circulating tumor cells in multiple myeloma by a PCR-based method. Leukemia. 1993 Nov;7(11):1879–1882. [PubMed] [Google Scholar]
  8. Gazitt Y., Reading C. C., Hoffman R., Wickrema A., Vesole D. H., Jagannath S., Condino J., Lee B., Barlogie B., Tricot G. Purified CD34+ Lin- Thy+ stem cells do not contain clonal myeloma cells. Blood. 1995 Jul 1;86(1):381–389. [PubMed] [Google Scholar]
  9. Gore M. E., Selby P. J., Viner C., Clark P. I., Meldrum M., Millar B., Bell J., Maitland J. A., Milan S., Judson I. R. Intensive treatment of multiple myeloma and criteria for complete remission. Lancet. 1989 Oct 14;2(8668):879–882. doi: 10.1016/s0140-6736(89)91548-1. [DOI] [PubMed] [Google Scholar]
  10. Gribben J. G., Freedman A. S., Neuberg D., Roy D. C., Blake K. W., Woo S. D., Grossbard M. L., Rabinowe S. N., Coral F., Freeman G. J. Immunologic purging of marrow assessed by PCR before autologous bone marrow transplantation for B-cell lymphoma. N Engl J Med. 1991 Nov 28;325(22):1525–1533. doi: 10.1056/NEJM199111283252201. [DOI] [PubMed] [Google Scholar]
  11. Hardingham J. E., Kotasek D., Sage R. E., Dobrovic A., Gooley T., Dale B. M. Molecular detection of residual lymphoma cells in peripheral blood stem cell harvests and following autologous transplantation. Bone Marrow Transplant. 1993 Jan;11(1):15–20. [PubMed] [Google Scholar]
  12. Ralph Q. M., Brisco M. J., Joshua D. E., Brown R., Gibson J., Morley A. A. Advancement of multiple myeloma from diagnosis through plateau phase to progression does not involve a new B-cell clone: evidence from the Ig heavy chain gene. Blood. 1993 Jul 1;82(1):202–206. [PubMed] [Google Scholar]
  13. Rill D. R., Santana V. M., Roberts W. M., Nilson T., Bowman L. C., Krance R. A., Heslop H. E., Moen R. C., Ihle J. N., Brenner M. K. Direct demonstration that autologous bone marrow transplantation for solid tumors can return a multiplicity of tumorigenic cells. Blood. 1994 Jul 15;84(2):380–383. [PubMed] [Google Scholar]
  14. Schiller G., Vescio R., Freytes C., Spitzer G., Sahebi F., Lee M., Wu C. H., Cao J., Lee J. C., Hong C. H. Transplantation of CD34+ peripheral blood progenitor cells after high-dose chemotherapy for patients with advanced multiple myeloma. Blood. 1995 Jul 1;86(1):390–397. [PubMed] [Google Scholar]
  15. Van Riet I., Heirman C., Lacor P., De Waele M., Thielemans K., Van Camp B. Detection of monoclonal B lymphocytes in bone marrow and peripheral blood of multiple myeloma patients by immunoglobulin gene rearrangement studies. Br J Haematol. 1989 Nov;73(3):289–295. doi: 10.1111/j.1365-2141.1989.tb07742.x. [DOI] [PubMed] [Google Scholar]
  16. Vescio R. A., Hong C. H., Cao J., Kim A., Schiller G. J., Lichtenstein A. K., Berenson R. J., Berenson J. R. The hematopoietic stem cell antigen, CD34, is not expressed on the malignant cells in multiple myeloma. Blood. 1994 Nov 15;84(10):3283–3290. [PubMed] [Google Scholar]
  17. Witzig T. E., Kyle R. A., Greipp P. R. Circulating peripheral blood plasma cells in multiple myeloma. Curr Top Microbiol Immunol. 1992;182:195–199. doi: 10.1007/978-3-642-77633-5_23. [DOI] [PubMed] [Google Scholar]

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