Skip to main content

The Lung Resistance Protein (LRP) Predicts Poor Outcome in Acute Myeloid Leukemia

  • Chapter
Drug Resistance in Leukemia and Lymphoma III

Abstract

To determine the clinical significance of the lung resistance protein (LRP) in acute myeloid leukemia (AML), we have studied LRP expression of leukemic blasts and its association with clinical outcome in patients with de novo AML. LRP expression of leukemic blasts was determined by immunocytochemistry by means of monoclonal antibody LRP-56. LRP expression at diagnosis was detected in 31 out of 86 (36%) patients and correlated with white blood cell count (p = 0.01). The complete remission rate of induction chemotherapy was 72% for all treated patients (n = 82). The complete remission rate was 81% for patients without LRP expression but only 55% for patients with LRP expression (p = 0.01). Overall survival and disease-free survival were estimated according to Kaplan-Meier in 82 and 59 patients, respectively. At a median follow-up of 16 months, median overall survival was 17 months for LRP-negative patients but only 8 months for LRP-positive patients (p = 0.006). Disease-free survival was 9 months for LRP-negative patients and 6 months for LRP-positive patients (p = 0.078). Thus LRP predicts for poor outcome indicating that the LRP gene is a clinically relevant drug resistance gene in AML.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Pastan I, Gottesman M. Multiple-drug resistance in human cancer. N Engl J Med 1987, 316, 1388–1393

    Article  PubMed  CAS  Google Scholar 

  2. Filipits M, Suchomel RW, Zöchbauer S, Malayeri R, Pirker R. Clinical relevance of drug resistance genes in malignant diseases. Leukemia 1996, 10(Suppl. 3), 10–17

    Google Scholar 

  3. Cole SPC, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AMV, Deeley RG. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 1992, 258, 1650–1654

    Article  PubMed  CAS  Google Scholar 

  4. Pirker R, Wallner J, Geissler K, Linkesch W, Haas OA, Bettelheim P, Hopfner M, Scherrer R, Valent P, Havelec L, Ludwig H, Lechner K. MDR1 gene expression and treatment outcome in acute myeloid leukemia. J Natl Cancer Inst 1991, 83, 708–712

    Article  PubMed  CAS  Google Scholar 

  5. Marie J-P, Zittoun R, Sikic BI. Multidrug resistance (mdr1) gene expression in adult acute leukemias: correlations with treatment outcome and in vitro drug sensitivity. Blood 1991, 78, 586–592

    PubMed  CAS  Google Scholar 

  6. 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, 79, 473–476

    PubMed  CAS  Google Scholar 

  7. Zöchbauer S, Gsur A, Brunner R, Kyrle PA, Lechner K, Pirker R. P-glycoprotein expression as unfavorable prognostic factor in acute myeloid leukemia. Leukemia 1994, 8, 974–977

    PubMed  Google Scholar 

  8. Filipits M, Suchomel RW, Zöchbauer S, Brunner R, Lechner K, Pirker R: Multidrug resistance-associated protein (MRP) in acute myeloid leukemia: no impact on treatment outcome. Clin Cancer Res 1997, 3, 1419–1425

    PubMed  CAS  Google Scholar 

  9. Filipits M, Stranzl T, Pohl G, Suchomel RW, Zöchbauer S, Brunner R, Lechner K, Pirker R. MRP expression in acute myeloid leukemia: an update. This volume (Chapter 16)

    Google Scholar 

  10. Kuss BJ, Deeley RG, Cole SPC, Willman CL, Kopecky KJ, Wolman SR, Eyre HJ, Lane SA, Nancarrow JK, Whitmore SA, Callen DF. Deletion of gene for multidrug resistance in acute myeloid leukaemia with inversion in chromosome 16: prognostic implications. Lancet 1994, 343, 1531–1534

    Article  PubMed  CAS  Google Scholar 

  11. Zöchbauer S, Haas OA, Schwarzinger I, Lechner K, Pirker R. Multidrug resistance in acute myeloid leukaemia with inversion in chromosome 16 or FAB M4Eo subtype. Lancet 1994, 344, 894

    Article  PubMed  Google Scholar 

  12. Scheper RJ, Broxterman HJ, Scheffer GL, Kaaijk P, Dalton WS, van Heijningen THM, van Kalken CK, Slovak ML, de Vries EGE, van der Valk P, Meijer CJLM, Pinedo HM. Overexpression of a Mr 110,000 vesicular protein in non-P-glycoprotein-mediated multidrug resistance. Cancer Res 1993, 53, 1475–1479

    PubMed  CAS  Google Scholar 

  13. Scheffer GL, Wijngaard PLJ, Flens MJ, Izquierdo MA, Slovak ML, Pinedo HM, Meijer CJLM, Clevers HC, Scheper RJ. The drug resistance-related protein LRP is the human major vault protein. Nat Med 1995, 1, 578–582

    Article  PubMed  CAS  Google Scholar 

  14. Kedersha NL, Miquel M-C, Bittner D, Rome LH. Vaults. II. Ribonucleoprotein structures are highly conserved among higher and lower eukaryotes. J Cell Biol 1990, 110, 895–901

    Article  PubMed  CAS  Google Scholar 

  15. Rome L, Kedersha N, Chugani D: Unlocking vaults: organelles in search of a function. Trends Cell Biol 1991, 1, 47–50

    Article  PubMed  CAS  Google Scholar 

  16. Izquierdo MA, Shoemaker RH, Flens MJ, Scheffer GL, Wu L, Prather TR, Scheper RJ. Overlapping phenotypes of multidrug resistance among panels of human cancer-cell lines. Int J Cancer 1996, 65, 230–237

    Article  PubMed  CAS  Google Scholar 

  17. Izquierdo MA, Scheffer GL, Flens MJ, Giaccone G, Broxterman HJ, Meijer CJLM, van der Valk P, Scheper RJ. Broad distribution of the multidrug resistance-related vault lung resistance protein in normal human tissues and tumors. Am J Pathol 1996, 148, 877–887

    PubMed  CAS  Google Scholar 

  18. Filipits M, Pohl G, Stranzl T, Suchomel RW, Scheper RJ, Jäger U, Geissler K, Lechner K, Pirker R. Expression of the lung resistance protein predicts poor outcome in de novo acute myeloid leukemia. Blood 1998, 91, 1508–1513

    PubMed  CAS  Google Scholar 

  19. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958, 53, 457–481

    Article  Google Scholar 

  20. List AF, Spier CS, Grogan TM, Johnson C, Roe DJ, Greer JP, Wolff SN, Broxterman HJ, Scheffer GL, Scheper RJ, Dalton WS. Overexpression of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia. Blood 1996, 87, 2464–2469

    PubMed  CAS  Google Scholar 

  21. Ghaddar HM, Plunkett W, Kantarjian HM, Pierce S, Freireich EJ, Keating MJ, Estey EH. Long-term results following treatment of newly-diagnosed acute myelogenous leukemia with continuous-infusion high-dose cytosine arabinoside. Leukemia 1994, 8, 1269–1274

    PubMed  CAS  Google Scholar 

  22. Lum BL, Fisher GA, Brophy NA, Yahanda AM, Adler KM, Kaubisch S, Halsey J, Sikic BI. Clinical trials of modulation of multidrug resistance. Cancer 1993, 72, 3502–3514

    Article  PubMed  CAS  Google Scholar 

  23. Pirker R, Keilhauer G, Raschack M, Lechner C, Ludwig H. Reversal of multi-drug resistance in human KB cell lines by structural analogs of verapamil. Int J Cancer 1990, 45, 916–919

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media New York

About this chapter

Cite this chapter

Pirker, R. et al. (1999). The Lung Resistance Protein (LRP) Predicts Poor Outcome in Acute Myeloid Leukemia. In: Kaspers, G.J.L., Pieters, R., Veerman, A.J.P. (eds) Drug Resistance in Leukemia and Lymphoma III. Advances in Experimental Medicine and Biology, vol 457. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4811-9_15

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-4811-9_15

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7180-9

  • Online ISBN: 978-1-4615-4811-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics