Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1993 Mar;67(3):430–435. doi: 10.1038/bjc.1993.83

P-glycoprotein expression in normal and reactive bone marrows.

S Hegewisch-Becker 1, M Fliegner 1, T Tsuruo 1, A Zander 1, W Zeller 1, D K Hossfeld 1
PMCID: PMC1968262  PMID: 8094974

Abstract

The expression of mdr1 gene product P-glycoprotein (P-gp) was investigated in 53 normal and reactive bone marrows by means of immunocytochemistry, using the monoclonal antibody (mAb) C219 and the alkaline phosphatase anti-alkaline phosphatase method. In a limited number of patients, data were confirmed by using the mAb MRK16 or a polymerase chain reaction assay for mdr1 gene expression. There was no history of prior chemotherapy or any malignancy in this group. Bone marrow aspirates were obtained as part of a routine diagnostic programme in bone marrow donors or in patients presenting with a variety of diagnoses such as unexplained gammopathy, fever, anaemia, other changes in peripheral blood smear, rheumatoid arthritis, vasculitis, or urticaria pigmentosa. Morphologically the bone marrow was normal in 23 patients, a megaloblastic erythropoiesis was seen in two patients and unspecific changes were seen in 28 patients. Twenty-seven of 53 samples were found to be positive for P-gp expression with the percentage of positive cells ranging from 2%-80% (mean = 24%). With a cutoff point of 10%, five of 23 normal (22%) and 13 of 28 reactive bone marrows (46%) were considered positive for P-gp expression. There was no obvious correlation between diagnosis or age and P-gp expression. Additional staining for the early surface marker CD-34 was performed in 12 samples, with none of them revealing more than 1% positivity. Since P-gp expression has so far been described only in CD-34 positive bone marrow cells, data suggest that P-gp expression may be reinduced in CD-34 negative cells under conditions which remain to be determined.

Full text

PDF
430

Images in this article

433Figure 1
on p.433
434Figure 2
on p.434

Selected References

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

  1. Arceci R. J., Baas F., Raponi R., Horwitz S. B., Housman D., Croop J. M. Multidrug resistance gene expression is controlled by steroid hormones in the secretory epithelium of the uterus. Mol Reprod Dev. 1990 Feb;25(2):101–109. doi: 10.1002/mrd.1080250202. [DOI] [PubMed] [Google Scholar]
  2. Bak M., Jr, Efferth T., Mickisch G., Mattern J., Volm M. Detection of drug resistance and P-glycoprotein in human renal cell carcinomas. Eur Urol. 1990;17(1):72–75. doi: 10.1159/000464005. [DOI] [PubMed] [Google Scholar]
  3. Campos L., Guyotat D., Archimbaud E., Calmard-Oriol P., Tsuruo T., Troncy J., Treille D., Fiere D. Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukemia cells at diagnosis. Blood. 1992 Jan 15;79(2):473–476. [PubMed] [Google Scholar]
  4. Chan H. S., Thorner P. S., Haddad G., Ling V. Immunohistochemical detection of P-glycoprotein: prognostic correlation in soft tissue sarcoma of childhood. J Clin Oncol. 1990 Apr;8(4):689–704. doi: 10.1200/JCO.1990.8.4.689. [DOI] [PubMed] [Google Scholar]
  5. Chaudhary P. M., Roninson I. B. Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells. Cell. 1991 Jul 12;66(1):85–94. doi: 10.1016/0092-8674(91)90141-k. [DOI] [PubMed] [Google Scholar]
  6. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  7. Civin C. I., Strauss L. C., Brovall C., Fackler M. J., Schwartz J. F., Shaper J. H. Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. J Immunol. 1984 Jul;133(1):157–165. [PubMed] [Google Scholar]
  8. Cordon-Cardo C., O'Brien J. P., Casals D., Rittman-Grauer L., Biedler J. L., Melamed M. R., Bertino J. R. Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc Natl Acad Sci U S A. 1989 Jan;86(2):695–698. doi: 10.1073/pnas.86.2.695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dalton W. S., Grogan T. M., Meltzer P. S., Scheper R. J., Durie B. G., Taylor C. W., Miller T. P., Salmon S. E. Drug-resistance in multiple myeloma and non-Hodgkin's lymphoma: detection of P-glycoprotein and potential circumvention by addition of verapamil to chemotherapy. J Clin Oncol. 1989 Apr;7(4):415–424. doi: 10.1200/JCO.1989.7.4.415. [DOI] [PubMed] [Google Scholar]
  10. Finstad C. L., Yin B. W., Gordon C. M., Federici M. G., Welt S., Lloyd K. O. Some monoclonal antibody reagents (C219 and JSB-1) to P-glycoprotein contain antibodies to blood group A carbohydrate determinants: a problem of quality control for immunohistochemical analysis. J Histochem Cytochem. 1991 Dec;39(12):1603–1610. doi: 10.1177/39.12.1682363. [DOI] [PubMed] [Google Scholar]
  11. Fojo A. T., Ueda K., Slamon D. J., Poplack D. G., Gottesman M. M., Pastan I. Expression of a multidrug-resistance gene in human tumors and tissues. Proc Natl Acad Sci U S A. 1987 Jan;84(1):265–269. doi: 10.1073/pnas.84.1.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hamada H., Tsuruo T. Functional role for the 170- to 180-kDa glycoprotein specific to drug-resistant tumor cells as revealed by monoclonal antibodies. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7785–7789. doi: 10.1073/pnas.83.20.7785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Holmes J. A., Jacobs A., Carter G., Whittaker J. A., Bentley D. P., Padua R. A. Is the mdr 1 gene relevant in chronic lymphocytic leukemia? Leukemia. 1990 Mar;4(3):216–218. [PubMed] [Google Scholar]
  14. Holmes J., Jacobs A., Carter G., Janowska-Wieczorek A., Padua R. A. Multidrug resistance in haemopoietic cell lines, myelodysplastic syndromes and acute myeloblastic leukaemia. Br J Haematol. 1989 May;72(1):40–44. doi: 10.1111/j.1365-2141.1989.tb07649.x. [DOI] [PubMed] [Google Scholar]
  15. Kartner N., Evernden-Porelle D., Bradley G., Ling V. Detection of P-glycoprotein in multidrug-resistant cell lines by monoclonal antibodies. 1985 Aug 29-Sep 4Nature. 316(6031):820–823. doi: 10.1038/316820a0. [DOI] [PubMed] [Google Scholar]
  16. Kartner N., Riordan J. R., Ling V. Cell surface P-glycoprotein associated with multidrug resistance in mammalian cell lines. Science. 1983 Sep 23;221(4617):1285–1288. doi: 10.1126/science.6137059. [DOI] [PubMed] [Google Scholar]
  17. Kuwazuru Y., Yoshimura A., Hanada S., Utsunomiya A., Makino T., Ishibashi K., Kodama M., Iwahashi M., Arima T., Akiyama S. Expression of the multidrug transporter, P-glycoprotein, in acute leukemia cells and correlation to clinical drug resistance. Cancer. 1990 Sep 1;66(5):868–873. doi: 10.1002/1097-0142(19900901)66:5<868::aid-cncr2820660510>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
  18. Neyfakh A. A., Serpinskaya A. S., Chervonsky A. V., Apasov S. G., Kazarov A. R. Multidrug-resistance phenotype of a subpopulation of T-lymphocytes without drug selection. Exp Cell Res. 1989 Dec;185(2):496–505. doi: 10.1016/0014-4827(89)90318-2. [DOI] [PubMed] [Google Scholar]
  19. Noonan K. E., Beck C., Holzmayer T. A., Chin J. E., Wunder J. S., Andrulis I. L., Gazdar A. F., Willman C. L., Griffith B., Von Hoff D. D. Quantitative analysis of MDR1 (multidrug resistance) gene expression in human tumors by polymerase chain reaction. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7160–7164. doi: 10.1073/pnas.87.18.7160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pirker R., Goldstein L. J., Ludwig H., Linkesch W., Lechner C., Gottesman M. M., Pastan I. Expression of a multidrug resistance gene in blast crisis of chronic myelogenous leukemia. Cancer Commun. 1989;1(2):141–144. doi: 10.3727/095535489820875354. [DOI] [PubMed] [Google Scholar]
  21. Pirker R., Wallner J., Geissler K., Linkesch W., Haas O. A., Bettelheim P., Hopfner M., Scherrer R., Valent P., Havelec L. MDR1 gene expression and treatment outcome in acute myeloid leukemia. J Natl Cancer Inst. 1991 May 15;83(10):708–712. doi: 10.1093/jnci/83.10.708. [DOI] [PubMed] [Google Scholar]
  22. Schneider J., Bak M., Efferth T., Kaufmann M., Mattern J., Volm M. P-glycoprotein expression in treated and untreated human breast cancer. Br J Cancer. 1989 Dec;60(6):815–818. doi: 10.1038/bjc.1989.372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Thiebaut F., Tsuruo T., Hamada H., Gottesman M. M., Pastan I., Willingham M. C. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7735–7738. doi: 10.1073/pnas.84.21.7735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Thiebaut F., Tsuruo T., Hamada H., Gottesman M. M., Pastan I., Willingham M. C. Immunohistochemical localization in normal tissues of different epitopes in the multidrug transport protein P170: evidence for localization in brain capillaries and crossreactivity of one antibody with a muscle protein. J Histochem Cytochem. 1989 Feb;37(2):159–164. doi: 10.1177/37.2.2463300. [DOI] [PubMed] [Google Scholar]
  25. Wishart G. C., Plumb J. A., Going J. J., McNicol A. M., McArdle C. S., Tsuruo T., Kaye S. B. P-glycoprotein expression in primary breast cancer detected by immunocytochemistry with two monoclonal antibodies. Br J Cancer. 1990 Nov;62(5):758–761. doi: 10.1038/bjc.1990.373. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES