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P-glycoprotein is an independent prognostic factor predicting relapse in childhood acute lymphoblastic leukaemia: results of a 6-year prospective study

Catharina Dhooge UGent, Barbara De Moerloose UGent, Genevieve Laureys UGent, Jozef Kint, A Ferster, Dirk De Bacquer UGent, Jan Philippé UGent and Yves Benoit UGent (1999) BRITISH JOURNAL OF HAEMATOLOGY. 105(3). p.676-683
abstract
P-glycoprotein (P-gp), a cellular drug-efflux pump, is thought to be one of the major causes of multidrug resistance (MDR) in malignancies, Since therapeutic strategies are being developed to circumvent drug resistance by inhibiting P-gp function, large prospective studies evaluating the clinical relevance of P-gp in childhood acute lymphoblastic leukaemia (ALL) are warranted. P-gp expression was evaluated over a period of 6 years in 102 consecutive patients with de novo childhood ALL and in 35 children with relapse of ALL. Bone marrow and blood smears were studied immunocytochemically with two monoclonal antibodies at initial diagnosis and at relapse. P-gp expression was found in 14 (14%) patients at initial diagnosis, After induction treatment, complete remission was achieved in 100/102 patients (98%), of whom 19 relapsed. Cumulative event-free survival was significantly higher in the P-gp-negative group compared with the P-gp-positive population (Logrank P=0.02). Multivariate analysis showed the results to be independent of age, WBC count and karyotype, and concomitantly underlined the importance of MDR1 phenotype detection in childhood ALL, P-gp expression was more frequently found at relapse (34%) than at primary diagnosis (P=0.01). In the relapsed patient group, P-gp-positive patients had a 2-fold greater risk for adverse clinical outcome than the P-gp-negative relapsed patients. P-gp expression was not induced by exposure to previous chemotherapy since the majority of P-gp-negative patients remained negative at relapse. P-glycoprotein expression in newly diagnosed childhood ALL is an independent adverse prognostic parameter with a predictive value for relapse.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
P-glycoprotein, MDR, childhood ALL, immunocytochemistry, ACUTE MYELOID-LEUKEMIA, MULTIDRUG-RESISTANCE, MALIGNANCIES, EXPRESSION, CHEMOTHERAPY, CYCLOSPORINE, ANTIBODIES, TUMORS, CANCER
journal title
BRITISH JOURNAL OF HAEMATOLOGY
Br. J. Haematol.
volume
105
issue
3
pages
676 - 683
Web of Science type
Article
Web of Science id
000081085100018
ISSN
0007-1048
DOI
10.1046/j.1365-2141.1999.01378.x
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
115020
handle
http://hdl.handle.net/1854/LU-115020
date created
2004-01-14 13:35:00
date last changed
2016-12-19 15:36:49
@article{115020,
  abstract     = {P-glycoprotein (P-gp), a cellular drug-efflux pump, is thought to be one of the major causes of multidrug resistance (MDR) in malignancies, Since therapeutic strategies are being developed to circumvent drug resistance by inhibiting P-gp function, large prospective studies evaluating the clinical relevance of P-gp in childhood acute lymphoblastic leukaemia (ALL) are warranted. P-gp expression was evaluated over a period of 6 years in 102 consecutive patients with de novo childhood ALL and in 35 children with relapse of ALL. Bone marrow and blood smears were studied immunocytochemically with two monoclonal antibodies at initial diagnosis and at relapse. P-gp expression was found in 14 (14\%) patients at initial diagnosis, After induction treatment, complete remission was achieved in 100/102 patients (98\%), of whom 19 relapsed. Cumulative event-free survival was significantly higher in the P-gp-negative group compared with the P-gp-positive population (Logrank P=0.02). Multivariate analysis showed the results to be independent of age, WBC count and karyotype, and concomitantly underlined the importance of MDR1 phenotype detection in childhood ALL, P-gp expression was more frequently found at relapse (34\%) than at primary diagnosis (P=0.01). In the relapsed patient group, P-gp-positive patients had a 2-fold greater risk for adverse clinical outcome than the P-gp-negative relapsed patients. P-gp expression was not induced by exposure to previous chemotherapy since the majority of P-gp-negative patients remained negative at relapse. P-glycoprotein expression in newly diagnosed childhood ALL is an independent adverse prognostic parameter with a predictive value for relapse.},
  author       = {Dhooge, Catharina and De Moerloose, Barbara and Laureys, Genevieve and Kint, Jozef and Ferster, A and De Bacquer, Dirk and Philipp{\'e}, Jan and Benoit, Yves},
  issn         = {0007-1048},
  journal      = {BRITISH JOURNAL OF HAEMATOLOGY},
  keyword      = {P-glycoprotein,MDR,childhood ALL,immunocytochemistry,ACUTE MYELOID-LEUKEMIA,MULTIDRUG-RESISTANCE,MALIGNANCIES,EXPRESSION,CHEMOTHERAPY,CYCLOSPORINE,ANTIBODIES,TUMORS,CANCER},
  language     = {eng},
  number       = {3},
  pages        = {676--683},
  title        = {P-glycoprotein is an independent prognostic factor predicting relapse in childhood acute lymphoblastic leukaemia: results of a 6-year prospective study},
  url          = {http://dx.doi.org/10.1046/j.1365-2141.1999.01378.x},
  volume       = {105},
  year         = {1999},
}

Chicago
Dhooge, Catharina, Barbara De Moerloose, Genevieve Laureys, Jozef Kint, A Ferster, Dirk De Bacquer, Jan Philippé, and Yves Benoit. 1999. “P-glycoprotein Is an Independent Prognostic Factor Predicting Relapse in Childhood Acute Lymphoblastic Leukaemia: Results of a 6-year Prospective Study.” British Journal of Haematology 105 (3): 676–683.
APA
Dhooge, C., De Moerloose, B., Laureys, G., Kint, J., Ferster, A., De Bacquer, D., Philippé, J., et al. (1999). P-glycoprotein is an independent prognostic factor predicting relapse in childhood acute lymphoblastic leukaemia: results of a 6-year prospective study. BRITISH JOURNAL OF HAEMATOLOGY, 105(3), 676–683.
Vancouver
1.
Dhooge C, De Moerloose B, Laureys G, Kint J, Ferster A, De Bacquer D, et al. P-glycoprotein is an independent prognostic factor predicting relapse in childhood acute lymphoblastic leukaemia: results of a 6-year prospective study. BRITISH JOURNAL OF HAEMATOLOGY. 1999;105(3):676–83.
MLA
Dhooge, Catharina, Barbara De Moerloose, Genevieve Laureys, et al. “P-glycoprotein Is an Independent Prognostic Factor Predicting Relapse in Childhood Acute Lymphoblastic Leukaemia: Results of a 6-year Prospective Study.” BRITISH JOURNAL OF HAEMATOLOGY 105.3 (1999): 676–683. Print.