Indian Journal of Hematology and Blood Transfusion

, Volume 27, Issue 3, pp 157–163 | Cite as

Expression of P-glycoprotein, Cyclin D1 and Ki-67 in Acute Lymphoblastic Leukemia: Relation with Induction Chemotherapy and Overall Survival

  • Ghada M. ElsayedEmail author
  • Manar M. Ismail
  • Manar M. Moneer
Original Article


Previous studies showed that non-cycling cells have a higher multidrug resistance (MDR) expression, which may be down-regulated by proliferation induction. Triggering these cells into proliferation down-regulates high MDR expression. The aim of this study was to determine the expression of P-glycoprotein (PGP) and cell cycle parameters (cyclin D1 and Ki-67) in acute lymphoblastic leukemia (ALL) at diagnosis, and to evaluate the correlation between the expressions of each marker, and the clinical significance of such expression with response to induction chemotherapy and overall survival. A total of 78 newly diagnosed ALL patients were enrolled in our study. PGP, cyclin D1 and Ki-67 were determined by flow cytometry. PGP expression was encountered in 10/78 (12.8%) of ALL cases. Cyclin D1 and Ki-67 were expressed in 16/77 (20.6%) and 27/76 (34.6%) of ALL cases, respectively. None of the parameters were associated with response to induction chemotherapy and overall survival. Based on the current analysis, we conclude that a joint immunophenotypic evaluation of PGP and cell cycle parameters like that adopted in this study is unlikely to reveal mechanisms of multidrug resistance associated with the clinical outcome.


P-gp Cyclin D1 Ki-67 Acute lymphoblastic leukemia (ALL) Multidrug resistance (MDR) 


  1. 1.
    Riordan JR, Ling V (1985) Genetic and biochemical characterization of multidrug resistance. Pharmacol Ther 28:51–75PubMedCrossRefGoogle Scholar
  2. 2.
    Huh HJ, Park CJ, Jang S, Seo EJ, Chi HS, Lee JH, Lee KH, Seo JJ, Moon HN, Ghim T (2006) Prognostic significance of multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression in acute leukemia. J Korean Med Sci 21(2):253–258PubMedCrossRefGoogle Scholar
  3. 3.
    Oh EJ, Kahng J, Kim Y, Kim M, Lim J, Kang CS et al (2003) Expression of functional markers in acute lymphoblastic leukemia. Leuk Res 27:903–908PubMedCrossRefGoogle Scholar
  4. 4.
    Smeets ME, Raymakers RA, Vierwinden G, Pennings AH, Wessels H, de Witte T (1999) Triggering noncycling hematopoietic progenitors and leukemic blasts to proliferate increases anthracycline retention and toxicity by down regulating multidrug resistance. Blood 94:2423–2424Google Scholar
  5. 5.
    Kaaijk P, Kaspers GJ, VanWering ER, Broekema GJ, Loonen AH, Hählen KE et al (2003) Cell proliferation is related to in vitro drug resistance in childhood acute leukemia. Br J Cancer 88:775–781PubMedCrossRefGoogle Scholar
  6. 6.
    Lacombe F, Belloc F (1996) Flow cytometry study of cell cycle, apoptosis and drug resistance in acute leukemia. Hematol Cell Ther 38:495–504PubMedCrossRefGoogle Scholar
  7. 7.
    Han K, Kahng J, Kim M, Lim J, Kim Y, Cho B et al (2000) Expression of functional markers in acute nonlymphoblastic leukemia. Acta Haematol 104:174–180PubMedCrossRefGoogle Scholar
  8. 8.
    Lee ST, Kim HJ, Kim SH (2006) Defining an optimal number of immunophenotypic markers for lineage assignment of acute leukemias based on the EGIL scoring system. Korean J Lab Med 26:393–399PubMedCrossRefGoogle Scholar
  9. 9.
    Bain B (2007) FAB and beyond. Leuk Lymphoma 48:2282–2283PubMedCrossRefGoogle Scholar
  10. 10.
    Ludwig WD, Rieder H, Bartram CR, Heinze B, Schwartz S, Gassmann W et al (1998) Immunophenotypic and genotypic features, clinical characteristics, and treatment outcome of adult pro-B acute lymphoblastic leukemia: results of the German multicenter trials GMALL 03/87 and 04/89. Blood 92:1898–1909PubMedGoogle Scholar
  11. 11.
    Michieli M, Daamani D, Ermacora A, Raspadori D, Michelutti A, Grimaz S et al (1997) P-gp (pgp) and lung resistance-related protein (LRP) expression and function in leukemic blast cells. Br J Hematol 96:356–365CrossRefGoogle Scholar
  12. 12.
    Elnenaei MO, Jadayel DM, Matutes E, Morilla R, Owusu-Ankomah K, Atkinson S et al (2001) Cyclin D1 by flowcytometry as a useful tool in the diagnosis of B-cell malignancies. Leuk Res 25:115–123PubMedCrossRefGoogle Scholar
  13. 13.
    Nowicki Miskowiak B, Kaczmarek-Kanold M (2002) Correlation between early treatment failure and Ki-67 antigen expression in blasts of children with acute lymphoblastic leukemia before commencing treatment. Oncology 62:55–59CrossRefGoogle Scholar
  14. 14.
    Wuchter C, Lenoid K, Ruppert V, Schrappe M, Buchner T, Schoch C et al (2000) Clinical significance of P-glycoprotein expression and function for response to induction chemotherapy, relapse rate and overall survival in acute leukemia. Hematologica 85:711–721Google Scholar
  15. 15.
    Kanerva J, Tiirikainen M, Makipernaa A, Riikonen P, Möttönen M, Salmi TT et al (1998) Multiple drug resistance mediated by P-glycoprotein is not a major factor in a slow response to therapy in childhood ALL. Pediatr Hematol Oncol 15:11–21PubMedCrossRefGoogle Scholar
  16. 16.
    Wattel E, Lepelley P, Meralt A, Guerci A, Chomienne C, Fenaux P (1996) Expression of the multidrug resistance p-gp in newly diagnosed adult acute lymphoblastic leukemia: absence of correlation with response to treatment. Leukemia 10:1164–1167PubMedGoogle Scholar
  17. 17.
    Tafuri A, Gregorj C, Petrucci MT, Ricciardi MR, Mancini M, Cimino G et al (2002) MDR1 protein expression is an independent predictor of complete remission in newly diagnosed adult acute lymphoblastic leukemia. Blood 100:974–998PubMedCrossRefGoogle Scholar
  18. 18.
    Goasguen JE, Dossot J-M, Fardel O, Le Mee F, Le Gall E, Leblay R et al (1993) Expression of multidrug resistance associated p-glycoprotein (p-170) in 59 cases of de novo acute lymphoblastic leukemia: prognostic implication. Blood 81:2394–2398PubMedGoogle Scholar
  19. 19.
    Sauerbrey A, Häfer R, Zintl F, Volm M (1999) Analysis of cyclin D1 in de novo and relapsed childhood acute lymphoblastic leukemia. Anticancer Res 19(1B):645–649PubMedGoogle Scholar
  20. 20.
    Oh EJ, Kahng J, Kim Y, Kim M, Lim J, Kang CS, Min WS, Cho B, Lee A, Lee KY, Kim WI, Shim SI, Han K (2003) Expression of functional markers in acute lymphoblastic leukemia. Leuk Res 27(10):903–908PubMedCrossRefGoogle Scholar
  21. 21.
    Aref S, Mabed M, El-Sherbiny M, Selim T, Metwaly A (2006) Cyclin D1 expression in acute leukemia. Hematology 11(1):31–34PubMedCrossRefGoogle Scholar
  22. 22.
    Jaroslav P, Martina H, Jiri S, Hana K, Petr S, Tomas K, Hulius M, Cedrik H (2005) Expression of cyclin D1, D2 and D3 and Ki-67 in human leukemia. Leuk Lymphoma 46:1605–1612PubMedCrossRefGoogle Scholar
  23. 23.
    Hedberg Y, Davoodi E, Roos G, Ljungberg B, Landberg G (1999) Cyclin-D1 expression in human renal-cell carcinoma. Cancer 84:268–272Google Scholar
  24. 24.
    Tsurusawa M, Ito M, Zha Z, Kawai S, Takasaki Y (1992) Cell-cycle-associated expression of proliferating cell nuclear antigen and Ki-67 reactive antigen of bone marrow blast cells in childhood acute leukemia. Leukemia 6(7):669–674PubMedGoogle Scholar
  25. 25.
    Volm M, Koomägi R, Stammler G, Rittgen W, Zintl F, Sauerbrey A (1997) Prognostic implications of cyclins (D1, E, A), cyclin-dependent kinases (CDK2, CDK4) and tumor-suppressor genes (pRB, p16INK4A) in childhood acute lymphoblastic leukemia. Int J Cancer 74(5):508–512PubMedCrossRefGoogle Scholar
  26. 26.
    Nagao K, Kikuchi A, Kawai Y, Kizaki M, Ikeda Y, Nishikawa T (1997) Skin infiltration in acute promyelocytic leukemia. Dermatology 194:168–171PubMedCrossRefGoogle Scholar

Copyright information

© Indian Society of Haematology & Transfusion Medicine 2011

Authors and Affiliations

  • Ghada M. Elsayed
    • 1
    Email author
  • Manar M. Ismail
    • 1
  • Manar M. Moneer
    • 2
  1. 1.Clinical Pathology DepartmentNational Cancer Institute, Cairo UniversityHiliopolis, CairoEgypt
  2. 2.Epidemiology and Medical Statistics DepartmentNational Cancer Institute, Cairo UniversityHiliopolis, CairoEgypt

Personalised recommendations