P-Glycoprotein Expression on Patients with Acute Lymphoblastic Leukemia
Abstract
Abstract
Objective: P-glycoprotein (P-gp) overexpression on neoplastic cells can deteriorate the therapeutic outcome on cancer patients.
P-gp plays important role on drug efficacy and toxicity. This research aimed to measure P-gp expression on children with Acute
Lymphoblastic Leukemia (ALL) on Sanglah Hospital, Denpasar. Method: Flowcytometry method was used to measure P-gp
expression level on Bone Marrow samples from pediatric patients (0-12 years old) who were newly diagnosed with ALL in
Sanglah Hospital. P-gp overexpression were based on the percentage of cell stained. Ten percent of P-gp expression were
considered as the cut-off value of P-gp overexpression. Result: On this study, 11 samples were obtained with the range value of
56-97% on P-gp expression. Conclusion: All 11 patients had P-gp overexpression.
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References
REFERENCES
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Kroetz, T. E. Klein, and R. B. Altman. (2011, March). Very
important pharmacogene summary: ABCB1 (MDR1, Pglycoprotein).
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https://www.ncbi.nlm.nih.gov/pubmed/20216335
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MDR1 Gene Polymorphisms and Clinical Relevance. Acta Genetica
Sinica. [Online]. 33 (2). pp. 93–104. Available:
http://www.sciencedirect.com
/science/article/pii/S0379417206600279?via%3Dihub
[3] K. L. Fung and M.M. Gotte. (2009, May). A synonymous
polymorphism in a common MDR1 (ABCB1) haplotype shapes
protein function. Biochim Biophys Acta. [Online]. 1794(5). pp. 860–
871. Available: https://www.ncbi.nlm.nih.gov/pubmed/19285158
[4] H.J. Broxterman. 1996. How to Probe Clinical Tumour Samples for
P-glycoprotein and Multidrug Resistance-associated Protein.
European Journal of Cancer. [Online]. 33A(6). pp. 1024-1033.
Available: https://www.ncbi.nlm.nih.gov /pubmed/8763344
[5] A. L. Dogan, A. Kars, H. Canpinar, D. Güç, M. Hayran, W. E. Criss,
E. Kansu. (2004). Prediction of Clinical Response to Chemotherapy
by In Vitro Chemosensitivity Assay In Acute Leukemia. Turkish
Journal of Cancer. [Online]. 34(2). pp. 75-80. Available:
http://www.turkjcancer.org/pdf/pdf_ TJC_367.pdf
[6] V. NÜssler, R. Pelka-Flescher, H. Zwierzina, C. Nerl, B. Beckert, F.
Gieseler, H. Diem, Ledderose G, E. Gullis, H. Sauer, W. Wilmanns.
> Journal of Health Sciences and Medicine UNUD Journals, Vol. 1 No. 1, February 2017
41
(1996, July). P-glycoprotein expression in patients with acute
leukemia-clinical relevance. Leukemia. [Online]. 10(Suppl 3). pp.
S23-S31. Available: https://www.ncbi.nlm.nih.gov/pubmed/8656697
[7] V. NÜssler, R. Pelka-Flescher, H. Zwierzina, C. Nerl, B. Beckert, E.
Gullis, F. Gieseler, S. Bock, R. Bartl, P. E. Petrides, et al. (1994).
Clinical Importance of P-glycoprotein-related resistance in Leukemia
and Myelodysplastic Syndromes-First Experience with Their
Reversal. Ann. Hematol. [Online]. 69 (Suppl 1). pp. S25-9.
Available: http://link.springer.com/article/10.1007/BF01757351
[8] I B. Mudita. (2007). Pola Penyakit dan Karakteristik Pasien Hemato
Onkologi Bagian Ilmu Kesehatan Anak Fakultas Kedokteran
Universitas Udayana / Rumah Sakit Sanglah Periode 2000-2005. Sari
Pediatri. [Online]. 9(1). pp. 13-16. Available:
https://www.researchgate.net/publication/312404291_Pola_Penyakit
_dan_Karakteristik_Pasien_Hemato_Onkologi_Bagian_Ilmu_Keseha
tan_Anak_Fakultas_Kedokteran_Universitas_UdayanaRS_Sanglah_
Denpasar_Periode_2000-2005
[9] S. V. Ambudkar, C. Kimchi-Sarfaty, Z. E. Sauna and M. M.
Gottesman. (2003). P-glycoprotein: from genomics to mechanism.
Oncogene. [Online]. 22. pp. 7468–7485. Available:
https://www.ncbi.nlm.nih.gov/pubmed/14576852
[10] J. M. Gow, L. M. Hodges, L. W. Chin, D. L. Kroetz. (2008).
Substrate – Dependent Effect of Human ABCB1 Coding
Polymorphisms. J Phamacol Exp Ther. [Online]. 325(2). pp. 435 -
442. Available: http://jpet.aspetjournals.org/content/jpet/325/2/435.
full.pdf
[11] C. Kimchi-Sarfathy, J. M. Oh, I. W. Kim, Z. E. Sauna, A. M.
Calcagno. S. V. Ambudkar, M. M. Gottesman. (2007). A Silent
Polymorphism in the MDR-1 Gene Changes Substrate Specificity.
Science. [Online]. 315. pp. 525-528. Available:
https://www.ncbi.nlm.nih.gov/pubmed/17185560
[12] N. N. Salama, Z. Yang, T. Bui, R. J. Ho. (2006). MDR 1 Haplotypes
Significantly Minimize Intracellular Uptake and Transcellular P-Gp
Substrate Transport in Recombinant LLC-PK1 Cells. Journal of
Pharmaceutical Sciences. [Online]. 95. pp. 2293 – 2308. Available:
https://www.ncbi.nlm.nih.gov/pubmed/16883550
[13] D. L. Kroetz, C. Pauli-Magnus, L. M. Hodges, C. C. Huang, M.
Kawamoto, S. J. John, D. Stryke, T. E. Ferrin, J. De Young, T.
Taylor, E. J. Carlson, I. Herskowitz, K. M. Giacomini, A. G. Clark.
(2003). Sequence Diversity And Haplotype Structure in Human
ABCB1 (MDR1, Multi Drug Resistance Transporter) Gene.
Pharmacogenetics. [Online]. 13. pp. 481-494. Available:
https://www.ncbi.nlm.nih.gov/pubmed/16883550
[14] M. K. Leabman, C. C. Huang, J. D. Young, E J. Carlson, T. R.
Taylor, D. L. M. Cruz, S. J John, D. Stryke, M. Kawamoto, T. J.
Urban, D. L. Kroetz, T. E. Ferrin, A. G. Clark, N. Risch, I.
Herskowitz, K. M. Giacomini. (2003). Natural Variation In Human
Membrane Transpoter Genes Reveals Evolutionary and Functional
Constrains. Proc Natl Acad Sci USA. [Online]. 100. pp. 5896 – 5901.
Available: http://www.pnas.org/content/100/10/5896.full.pdf
[15] S. Hoffmeyer, O. Burk, O Richter, H. P. Arnold, J. Brockmoller, A.
Johne, I. Cascorbi, T. Gerloff, I. Roots, M. Eichelbaum, U.
Brinkmann. (2000). Functional polymorphisms of the human
multidrug resistance gene: multiple sequence variations and
correlation of one allele with P-glycoprotein expression and activity
in vivo. Proc NatlAcad Sci USA. [Online]. 97. pp. 3473-3478.
Available: https://www.ncbi.nlm.nih.gov/pubmed/10716719
[16] R. B. Kim, B. F. Leake, E. F. Choo, G. K. Dresser, S. V. Kubba, U. I.
Schwarz, A. Taylor, H. G. Xie, J. McKinsey, S. Zhou, L. B. Lan, J.
D. Schuetz, E. G. Schuetz, G. R. Wilkinson. (2001). Identification of
functionally variant MDR1 alleles among European Americans and
African Americans. Clin Pharmacol Ther. [Online]. 70. pp. 189-199.
Available: https://www.ncbi.nlm.nih.gov/pubmed/11503014
[17] M. M. Ameyaw, F. Regateiro, T. Li, X. Liu, M. Tariq, A. Mobarek,
N. Thornton, G. O. Folayan, J. Githang’a, A. Indalo, D. Ofori-Adjei,
D. A. Price-Evans, H. L. McLeod. (2001). MDR1 pharmacogenetics:
frequency of the C3435T mutation in exon 26 is significantly
influenced by ethnicity. Pharmacogenetics. [Online]. 11. pp. 217-
221. Available: https://www.ncbi.nlm.nih.gov/pubmed/11337937
[18] M. Saidijam, H. Mahjub, N. Shabab, R. Yadegarazari, (2015).
Simultaneous Analyisis of Multidrug Resistance 1 (MDR-1)
C3435T, G 2677 T/A, and C1236T Genotype in Hamadan City
Population, West of Iran. Iranian Biomedical Journal. [Online].
19(1). pp. 57-62. Available:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322234/
[19] A. J. Brambilla-Tapia. (2013). MDR 1 (ABCB1) polymorphisms:
functional effects and Clininal Implications. Revista de Investigacon
Clinica. [Online]. 65(5). pp. 445 –454. Available:
https://www.ncbi.nlm.nih. gov/pubmed/24687344
[20] K. Tang, S. M. Ngoi, P. C. Gwee, J. M. Chua, E. J. Lee, S. S. Chong
and C. G. Lee. (2002). Distinct Haplotype Profiles And Strong
Linkage Disequilibrium At The MDR1 Multidrug Transporter Gene
Locus In Three Ethnic Asian Populations. Pharmacogenetics.
[Online]. 12. pp. 437–450. Available:https://www.ncbi.nlm.nih.gov/
pubmed/12172212
[21] C. J. Chen, D. Clark, K. Ueda, I. Pastan, M. M. Gottesman and I. B.
Roninson. (1990, January). Genomic Organization of Human
Multidrug Resistance (MDR1) Gene and Origin of P-Glycoprotein. J
Biol Chem. [Online]. 265(1). pp. 506-514. Available:
https://www.ncbi.nlm.nih.gov/pubmed/1967175
[22] D. Vivona, L. T. Lima, A. C. Rodrigues, C. T. Bueno, G. K. S.
Alcantara, L. S. R. Barbos, V. T. D. M. Hungria, C. S. Chiattone, M.
D. L. L. D. Chauffaille, E. M. Guerra-Shinohara. (2014). ABCB1
Haplotype are Associated with P-gp Activity and Affect a Major
Molecular Response in Chronic Myeloid Leukemia Patients Treated
with A standard Dose of Imatinib. Oncology Letters. [Online]. 7. pp.
1313-1319. Available: https://www.ncbi.nlm.nih.gov/pubmed/24660
038
[23] K. L. Fung and M. M. Gottesman. (1794). A synonymous
polymorphism in a common MDR1 (ABCB1) haplotype shapes
protein function. Biochim Biophys Acta. 1794. pp. 860-871.
[24] A. Ashariati, (2008, October). Polymorphism C3435T of The MDR-
1 Gene Predict Response to Preoperative Chemotherapy in Locally
Advanced Breast Cancer with Her 2/ neu Expression. Acta med
Indones, [Online]. 40(4). pp. 187-91. Available:
https://www.ncbi.nlm.nih.gov/pubmed/19151448
[25] A. F. List, K. J. Kopecky, C. L. Willman, D. R. Head, D. L. Persons,
M. L. Slovak, R. Dorr, C. Karanes, H. E. Hynes, J. H. Doroshow, M.
Shurafa and F. R. Appelbaum. (2001). Benefit of cyclosporine
modulation of drug resistance in patients with poor-risk acute
myeloid leukemia: a Southwest Oncology Group study. Blood,
[Online]. 98. pp. 3212–3220. Available:
https://www.ncbi.nlm.nih.gov/pubmed ?cmd=Link &dbFrom
=PubMed&from_uid=8874180
[1] L. M. Hodges, S. M. Markova, L. W. Chinn, J. M. Gow, D. L.
Kroetz, T. E. Klein, and R. B. Altman. (2011, March). Very
important pharmacogene summary: ABCB1 (MDR1, Pglycoprotein).
Pharmacogenet Genomics. [Online]. 21(3). pp. 152–161. Available:
https://www.ncbi.nlm.nih.gov/pubmed/20216335
[2] L. Yan-Hong, W. Yong-Hua, L. Yan, Y. Ling. (2006, February).
MDR1 Gene Polymorphisms and Clinical Relevance. Acta Genetica
Sinica. [Online]. 33 (2). pp. 93–104. Available:
http://www.sciencedirect.com
/science/article/pii/S0379417206600279?via%3Dihub
[3] K. L. Fung and M.M. Gotte. (2009, May). A synonymous
polymorphism in a common MDR1 (ABCB1) haplotype shapes
protein function. Biochim Biophys Acta. [Online]. 1794(5). pp. 860–
871. Available: https://www.ncbi.nlm.nih.gov/pubmed/19285158
[4] H.J. Broxterman. 1996. How to Probe Clinical Tumour Samples for
P-glycoprotein and Multidrug Resistance-associated Protein.
European Journal of Cancer. [Online]. 33A(6). pp. 1024-1033.
Available: https://www.ncbi.nlm.nih.gov /pubmed/8763344
[5] A. L. Dogan, A. Kars, H. Canpinar, D. Güç, M. Hayran, W. E. Criss,
E. Kansu. (2004). Prediction of Clinical Response to Chemotherapy
by In Vitro Chemosensitivity Assay In Acute Leukemia. Turkish
Journal of Cancer. [Online]. 34(2). pp. 75-80. Available:
http://www.turkjcancer.org/pdf/pdf_ TJC_367.pdf
[6] V. NÜssler, R. Pelka-Flescher, H. Zwierzina, C. Nerl, B. Beckert, F.
Gieseler, H. Diem, Ledderose G, E. Gullis, H. Sauer, W. Wilmanns.
> Journal of Health Sciences and Medicine UNUD Journals, Vol. 1 No. 1, February 2017
41
(1996, July). P-glycoprotein expression in patients with acute
leukemia-clinical relevance. Leukemia. [Online]. 10(Suppl 3). pp.
S23-S31. Available: https://www.ncbi.nlm.nih.gov/pubmed/8656697
[7] V. NÜssler, R. Pelka-Flescher, H. Zwierzina, C. Nerl, B. Beckert, E.
Gullis, F. Gieseler, S. Bock, R. Bartl, P. E. Petrides, et al. (1994).
Clinical Importance of P-glycoprotein-related resistance in Leukemia
and Myelodysplastic Syndromes-First Experience with Their
Reversal. Ann. Hematol. [Online]. 69 (Suppl 1). pp. S25-9.
Available: http://link.springer.com/article/10.1007/BF01757351
[8] I B. Mudita. (2007). Pola Penyakit dan Karakteristik Pasien Hemato
Onkologi Bagian Ilmu Kesehatan Anak Fakultas Kedokteran
Universitas Udayana / Rumah Sakit Sanglah Periode 2000-2005. Sari
Pediatri. [Online]. 9(1). pp. 13-16. Available:
https://www.researchgate.net/publication/312404291_Pola_Penyakit
_dan_Karakteristik_Pasien_Hemato_Onkologi_Bagian_Ilmu_Keseha
tan_Anak_Fakultas_Kedokteran_Universitas_UdayanaRS_Sanglah_
Denpasar_Periode_2000-2005
[9] S. V. Ambudkar, C. Kimchi-Sarfaty, Z. E. Sauna and M. M.
Gottesman. (2003). P-glycoprotein: from genomics to mechanism.
Oncogene. [Online]. 22. pp. 7468–7485. Available:
https://www.ncbi.nlm.nih.gov/pubmed/14576852
[10] J. M. Gow, L. M. Hodges, L. W. Chin, D. L. Kroetz. (2008).
Substrate – Dependent Effect of Human ABCB1 Coding
Polymorphisms. J Phamacol Exp Ther. [Online]. 325(2). pp. 435 -
442. Available: http://jpet.aspetjournals.org/content/jpet/325/2/435.
full.pdf
[11] C. Kimchi-Sarfathy, J. M. Oh, I. W. Kim, Z. E. Sauna, A. M.
Calcagno. S. V. Ambudkar, M. M. Gottesman. (2007). A Silent
Polymorphism in the MDR-1 Gene Changes Substrate Specificity.
Science. [Online]. 315. pp. 525-528. Available:
https://www.ncbi.nlm.nih.gov/pubmed/17185560
[12] N. N. Salama, Z. Yang, T. Bui, R. J. Ho. (2006). MDR 1 Haplotypes
Significantly Minimize Intracellular Uptake and Transcellular P-Gp
Substrate Transport in Recombinant LLC-PK1 Cells. Journal of
Pharmaceutical Sciences. [Online]. 95. pp. 2293 – 2308. Available:
https://www.ncbi.nlm.nih.gov/pubmed/16883550
[13] D. L. Kroetz, C. Pauli-Magnus, L. M. Hodges, C. C. Huang, M.
Kawamoto, S. J. John, D. Stryke, T. E. Ferrin, J. De Young, T.
Taylor, E. J. Carlson, I. Herskowitz, K. M. Giacomini, A. G. Clark.
(2003). Sequence Diversity And Haplotype Structure in Human
ABCB1 (MDR1, Multi Drug Resistance Transporter) Gene.
Pharmacogenetics. [Online]. 13. pp. 481-494. Available:
https://www.ncbi.nlm.nih.gov/pubmed/16883550
[14] M. K. Leabman, C. C. Huang, J. D. Young, E J. Carlson, T. R.
Taylor, D. L. M. Cruz, S. J John, D. Stryke, M. Kawamoto, T. J.
Urban, D. L. Kroetz, T. E. Ferrin, A. G. Clark, N. Risch, I.
Herskowitz, K. M. Giacomini. (2003). Natural Variation In Human
Membrane Transpoter Genes Reveals Evolutionary and Functional
Constrains. Proc Natl Acad Sci USA. [Online]. 100. pp. 5896 – 5901.
Available: http://www.pnas.org/content/100/10/5896.full.pdf
[15] S. Hoffmeyer, O. Burk, O Richter, H. P. Arnold, J. Brockmoller, A.
Johne, I. Cascorbi, T. Gerloff, I. Roots, M. Eichelbaum, U.
Brinkmann. (2000). Functional polymorphisms of the human
multidrug resistance gene: multiple sequence variations and
correlation of one allele with P-glycoprotein expression and activity
in vivo. Proc NatlAcad Sci USA. [Online]. 97. pp. 3473-3478.
Available: https://www.ncbi.nlm.nih.gov/pubmed/10716719
[16] R. B. Kim, B. F. Leake, E. F. Choo, G. K. Dresser, S. V. Kubba, U. I.
Schwarz, A. Taylor, H. G. Xie, J. McKinsey, S. Zhou, L. B. Lan, J.
D. Schuetz, E. G. Schuetz, G. R. Wilkinson. (2001). Identification of
functionally variant MDR1 alleles among European Americans and
African Americans. Clin Pharmacol Ther. [Online]. 70. pp. 189-199.
Available: https://www.ncbi.nlm.nih.gov/pubmed/11503014
[17] M. M. Ameyaw, F. Regateiro, T. Li, X. Liu, M. Tariq, A. Mobarek,
N. Thornton, G. O. Folayan, J. Githang’a, A. Indalo, D. Ofori-Adjei,
D. A. Price-Evans, H. L. McLeod. (2001). MDR1 pharmacogenetics:
frequency of the C3435T mutation in exon 26 is significantly
influenced by ethnicity. Pharmacogenetics. [Online]. 11. pp. 217-
221. Available: https://www.ncbi.nlm.nih.gov/pubmed/11337937
[18] M. Saidijam, H. Mahjub, N. Shabab, R. Yadegarazari, (2015).
Simultaneous Analyisis of Multidrug Resistance 1 (MDR-1)
C3435T, G 2677 T/A, and C1236T Genotype in Hamadan City
Population, West of Iran. Iranian Biomedical Journal. [Online].
19(1). pp. 57-62. Available:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322234/
[19] A. J. Brambilla-Tapia. (2013). MDR 1 (ABCB1) polymorphisms:
functional effects and Clininal Implications. Revista de Investigacon
Clinica. [Online]. 65(5). pp. 445 –454. Available:
https://www.ncbi.nlm.nih. gov/pubmed/24687344
[20] K. Tang, S. M. Ngoi, P. C. Gwee, J. M. Chua, E. J. Lee, S. S. Chong
and C. G. Lee. (2002). Distinct Haplotype Profiles And Strong
Linkage Disequilibrium At The MDR1 Multidrug Transporter Gene
Locus In Three Ethnic Asian Populations. Pharmacogenetics.
[Online]. 12. pp. 437–450. Available:https://www.ncbi.nlm.nih.gov/
pubmed/12172212
[21] C. J. Chen, D. Clark, K. Ueda, I. Pastan, M. M. Gottesman and I. B.
Roninson. (1990, January). Genomic Organization of Human
Multidrug Resistance (MDR1) Gene and Origin of P-Glycoprotein. J
Biol Chem. [Online]. 265(1). pp. 506-514. Available:
https://www.ncbi.nlm.nih.gov/pubmed/1967175
[22] D. Vivona, L. T. Lima, A. C. Rodrigues, C. T. Bueno, G. K. S.
Alcantara, L. S. R. Barbos, V. T. D. M. Hungria, C. S. Chiattone, M.
D. L. L. D. Chauffaille, E. M. Guerra-Shinohara. (2014). ABCB1
Haplotype are Associated with P-gp Activity and Affect a Major
Molecular Response in Chronic Myeloid Leukemia Patients Treated
with A standard Dose of Imatinib. Oncology Letters. [Online]. 7. pp.
1313-1319. Available: https://www.ncbi.nlm.nih.gov/pubmed/24660
038
[23] K. L. Fung and M. M. Gottesman. (1794). A synonymous
polymorphism in a common MDR1 (ABCB1) haplotype shapes
protein function. Biochim Biophys Acta. 1794. pp. 860-871.
[24] A. Ashariati, (2008, October). Polymorphism C3435T of The MDR-
1 Gene Predict Response to Preoperative Chemotherapy in Locally
Advanced Breast Cancer with Her 2/ neu Expression. Acta med
Indones, [Online]. 40(4). pp. 187-91. Available:
https://www.ncbi.nlm.nih.gov/pubmed/19151448
[25] A. F. List, K. J. Kopecky, C. L. Willman, D. R. Head, D. L. Persons,
M. L. Slovak, R. Dorr, C. Karanes, H. E. Hynes, J. H. Doroshow, M.
Shurafa and F. R. Appelbaum. (2001). Benefit of cyclosporine
modulation of drug resistance in patients with poor-risk acute
myeloid leukemia: a Southwest Oncology Group study. Blood,
[Online]. 98. pp. 3212–3220. Available:
https://www.ncbi.nlm.nih.gov/pubmed ?cmd=Link &dbFrom
=PubMed&from_uid=8874180
Published
2017-02-01
How to Cite
NIIRURI, R. et al.
P-Glycoprotein Expression on Patients with Acute Lymphoblastic Leukemia.
Journal of Health Sciences and Medicine, [S.l.], v. 1, n. 1, p. 39-41, feb. 2017.
ISSN 2622-0555.
Available at: <https://ojs.unud.ac.id/index.php/jhsm/article/view/34823>. Date accessed: 07 may 2024.
doi: https://doi.org/10.24843/JHSM.2017.v01.i01.p10.
Section
Articles
