Yıl: 2022 Cilt: 10 Sayı: 6 Sayfa Aralığı: 691 - 697 Metin Dili: İngilizce DOI: 10.14235/bas.galenos.2021.6669 İndeks Tarihi: 05-05-2023

The Evaluation of Multidrug Resistance-Related Protein 1 as a Prognostic Factor in the Pediatric B-cell Acute Lymphoblastic Leukemia: A Pilot Study

Öz:
Objective: Acute lymphoblastic leukemia (ALL) is the most prevalent type of cancer in children. Minimal residual disease (MRD) is still the most important indicator of clinical results and relapse after chemotherapy. Multidrug resistance is the main obstacle to successful treatment. Multidrug resistance-related protein 1 (MRP1) may play a key role in throwing the chemical drug out of cells leading to therapy resistance. This study aims to detect MRP1 protein in the bone marrow cells of children with B-ALL and determine its value as a prognostic factor in comparison with other factors such as DNA index and MRD obtained by flow cytometric measurement. Methods: Bone marrow samples were obtained from children who are diagnosed as B-ALL (n=20) at day 0 (diagnosis) and 15 of therapy. Risk groups’ classification is based on discrimination of age and white cell count on day 0. The expressions of MRP1 levels and DNA index at diagnosis and MRD on the 15th day of treatment in the bone marrow were detected by using flow cytometry. The B-ALL blast cells were stained using anti-CD10, -CD19, -CD20, -CD34, -CD45 monoclonal antibodies. MRP1 content of cells was detected in an intracellular manner. Results: There was no statistically significant difference in MRP1 expression between risk groups and the other prognostic factor as Flow MRD and DNA index. Conclusion: The utilization of MRP1 as a predictive factor may not provide information on the B-ALL prognosis. Our results can help to better understand the nature of MRP1 in B-ALL patients.
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Öz:
Amaç: Akut lenfoblastik lösemi (ALL), çocuklarda en sık görülen kanser türüdür. Kemoterapinin ardından, minimal kalıntı hastalık (MRD) hala klinik sonuçların ve nüksün en önemli göstergesidir. Çoklu ilaç direnci başarılı tedavinin önündeki ana engeldir. Çoklu ilaç direnci ile ilişkili protein 1 (MRP1) kimyasal ilacın hücrelerden dışarı atılmasında anahtar rol oynayabilir ve tedaviye dirence neden olabilir. Bu çalışmanın amacı, B-hücre ALL’li çocukların kemik iliğinden alınan hücrelerde MRP1 proteinini saptamak ve akan hücre ölçer ile elde edilmiş DNA indeksi ve MRD gibi diğer faktörlerle karşılaştırılarak MRP1’in prognostik bir faktör olarak değerini belirlemektir. Yöntemler: B-ALL (n=20) tanılı çocuklardan tedavinin 0. (tanı anı) ve 15. gününde kemik iliği örnekleri alındı. Risk grupları tanı anındaki yaş ve beyaz hücre sayısına göre ayrılmıştır. Kemik iliğinde tanı anındaki MRP1 düzeyleri ve DNA indeksi ve tedavinin 15. gününde MRD düzeyi akan hücre ölçer kullanılarak tespit edildi. B-ALL blast hücreleri anti-CD10, -CD19, -CD20, -CD34, -CD45 monoklonal antikorlar kullanılarak boyanmıştır. Hücrelerinin MRP1 içeriği hücre içi boyama yöntemi ile belirlenmiştir. Bulgular: Risk grupları ile diğer prognostik faktörler flow MRD ve DNA indeks arasında MRP1 ekspresyonu açısından istatistiksel olarak anlamlı bir fark yoktu. Sonuç: MRP-1’in protein seviyeleri B-ALL prognozu hakkında bilgi sağlamayabilir. Sonuçlarımız, B-ALL hastalarında MRP-1’in doğasını daha iyi anlamaya yardımcı olabilir.
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Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Pizzo PA, Poplack DG. Principles and practice of pediatric oncology. 7th ed. Philadelphia: Lippincott Williams and Wilkins; 2015.
  • 2. Tejashri P, Raskar GVB. Robust Segmentation Method for Acute Lymphoblastic Leukemia Detection. International Journal of Advanced Research in Computer Science and Software Engineering 2015;5:632-6.
  • 3. Cobaleda C, Sánchez-García I. B-cell acute lymphoblastic leukemia: towards understanding its cellular origin. BioEssays 2009;31:600-9.
  • 4. Pui CH. Childhood leukemias. N Engl J Med 1995;332:1618-30.
  • 5. Smith M, Arthur D, Camitta B, Carroll AJ, Crist W, Gaynon P, et al. Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia. J Clin Oncol 1996;14:18-24.
  • 6. Williams DL, Tsiatis A, Brodeur GM, Look AT, Melvin SL, Bowman WP, et al. Prognostic importance of chromosome number in 136 untreated children with acute lymphoblastic leukemia. Blood 1982;60:864-71.
  • 7. Trueworthy R, Shuster J, Look T, Crist W, Borowitz M, Carroll A, et al. Ploidy of lymphoblasts is the strongest predictor of treatment outcome in B-progenitor cell acute lymphoblastic leukemia of childhood: a Pediatric Oncology Group study. J Clin Oncol 1992;10:606-13.
  • 8. Conter V, Bartram CR, Valsecchi MG, Schrauder A, Panzer- Grümayer R, Möricke A, et al. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood 2010;115:3206-14.
  • 9. Du Y, Chen B. Detection approaches for multidrug resistance genes of leukemia. Drug Des Devel Ther 2017;11:1255-61.
  • 10. El-Sharnouby JA, Abou El-Enein AM, El Ghannam DM, El- Shanshory MR, Hagag AA, Yahia S, et al. Expression of lung resistance protein and multidrug resistance-related protein (MRP1) in pediatric acute lymphoblastic leukemia. J Oncol Pharm Pract 2010;16:179-88.
  • 11. Vindeløv LL, Christensen IJ, Nissen NI. A detergent-trypsin method for the preparation of nuclei for flow cytometric DNA analysis. Cytometry 1983;3:323-7.
  • 12. M Abu Taleb F, Abdel-Wahid R, Abdel-azeez M, A Zidan H, Esh A, Sead. Flow Cytometric Analysis of Nuclear DNA Ploidy and Proliferative Activity in Acute Lymphoblastic Leukemia. Journal of the Egyptian Nat Cancer Inst 2002;14:303-10.
  • 13. Dworzak MN, Gaipa G, Ratei R, Veltroni M, Schumich A, Maglia O, et al. Standardization of flow cytometric minimal residual disease evaluation in acute lymphoblastic leukemia: Multicentric assessment is feasible. Cytometry B Clin Cytom 2008;74:331-40.
  • 14. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4 ed. Lyon, France: IARC Press; 2008.
  • 15. Cai BL, Li Y, Shen LL, Zhao JL, Liu Y, Wu JZ, et al. Nuclear Multidrug resistance-related Protein 1 Is Highly Associated with Better Prognosis of Human Mucoepidermoid Carcinoma through the Suppression of Cell Proliferation, Migration, and Invasion. PloS One 2016;11:e0148223.
  • 16. Taheri M, Motalebzadeh J, Mahjoubi F. Expression of LRP Gene in Breast Cancer Patients Correlated with MRP1 as Two Independent Predictive Biomarkers in Breast Cancer. Asian Pac J Cancer Prev 2018;19:3111-5.
  • 17. Gunduz E, Dincer M, Yildiz G, Bal C, Gulbas Z. The frequency and clinical relevance of multidrug resistance protein expression in patients with lymphoma. Turk J Haematol 2012;29:120-9.
  • 18. Schneider E, Cowan KH, Bader H, Toomey S, Schwartz GN, Karp JE, et al. Increased expression of the multidrug resistance-associated protein gene in relapsed acute leukemia. Blood 1995;85:186-93.
  • 19. Ogretmen B, Barredo JC, Safa AR. Increased expression of lung resistance-related protein and multidrug resistance-associated protein messenger RNA in childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol 2000;22:45-9.
  • 20. Plasschaert SL, de Bont ES, Boezen M, vander Kolk DM, Daenen SM, Faber KN, et al. Expression of multidrug resistanceassociated proteins predicts prognosis in childhood and adult acute lymphoblastic leukemia. Clin Cancer Res 2005;11:8661-8.
  • 21. Huh HJ, Park CJ, Jang S, Seo EJ, Chi HS, Lee JH, et al. 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 2006;21:253-8.
  • 22. Gurbuxani S, Singh Arya L, Raina V, Sazawal S, Khattar A, Magrath I, et al. Significance of MDR1, MRP1, GSTpi and GSTmu mRNA expression in acute lymphoblastic leukemia in Indian patients. Cancer Lett 2001;167:73-83.
  • 23. Chauhan PS, Bhushan B, Singh LC, Mishra AK, Saluja S, Mittal V, et al. Expression of genes related to multiple drug resistance and apoptosis in acute leukemia: response to induction chemotherapy. Exp Mol Pathol 2012;92:44-9.
  • 24. Kakihara T, Tanaka A, Watanabe A, Yamamoto K, Kanto K, Kataoka S, et al. Expression of multidrug resistance-related genes does not contribute to risk factors in newly diagnosed childhood acute lymphoblastic leukemia. Pediatr Int 1999;41:641-7.
  • 25. Sauerbrey A, Voigt A, Wittig S, Häfer R, Zintl F. Messenger RNA analysis of the multidrug resistance-related protein (MRP1) and the lung resistance protein (LRP) in de novo and relapsed childhood acute lymphoblastic leukemia. Leuk Lymphoma 2002;43:875-9.
  • 26. Valera ET, Scrideli CA, Queiroz RG, Mori BM, Tone LG. Multiple drug resistance protein (MDR-1), multidrug resistance-related protein (MRP), and lung resistance protein (LRP) gene expression in childhood acute lymphoblastic leukemia. Sao Paulo Med J 2004;122:166-71.
  • 27. Fedasenka UU, Shman TV, Savitski VP, Belevcev MV. Expression of MDR1, LRP, BCRP, and Bcl-2 genes at diagnosis of childhood all: comparison with MRD status after induction therapy. Exp Oncol 2008;30:248-52.
  • 28. Olson DP, Taylor BJ, La M, Sather H, Reaman GH, Ivy SP. The prognostic significance of P-glycoprotein, multidrug resistance-related protein 1 and lung resistance protein in pediatric acute lymphoblastic leukemia: a retrospective study of 295 newly diagnosed patients by the Children’s Oncology Group. Leuk Lymphoma 2005;46:681-91.
  • 29. Fujimaki S, Funato T, Harigae H, Fujiwara J, Kameoka J, Meguro K, et al. Quantitative analysis of an MDR1 transcript for prediction of drug resistance in acute leukemia. Clin Chem 2002;48:811-7.
  • 30. Den Boer ML, Pieters R, Kazemier KM, Janka-Schaub GE, Henze G, Creutzig U, et al. Different expression of glutathione S-transferase alpha, mu and pi in childhood acute lymphoblastic and myeloid leukemia. Br J Haematol 1999;104:321-7.
  • 31. Borowitz MJ, Devidas M, Hunger SP, Bowman WP, Carroll AJ, Carroll WL, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children’s Oncology Group study. Blood 2008;111:5477-85.
  • 32. Lustosa de Sousa DW, de Almeida Ferreira FV, Cavalcante Félix FH, de Oliveira Lopes MV. Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival. Rev Bras Hematol Hemoter 2015;37:223-9.
  • 33. Drach J, Zhao S, Drach D, Korbling M, Engel H, Andreeff M. Expression of MDR1 by normal bone marrow cells and its implication for leukemic hematopoiesis. Leuk Lymphoma 1995;16:419-24.
  • 34. Shuster JJ, Wacker P, Pullen J, Humbert J, Land VJ, Mahoney DH, et al. Prognostic significance of sex in childhood B-precursor acute lymphoblastic leukemia: a Pediatric Oncology Group Study. J Clin Oncol 1998;16:2854-63.
APA A, gelmez m, Tahrali I, Aydogan M, DENİZ G, Cinar S (2022). The Evaluation of Multidrug Resistance-Related Protein 1 as a Prognostic Factor in the Pediatric B-cell Acute Lymphoblastic Leukemia: A Pilot Study. , 691 - 697. 10.14235/bas.galenos.2021.6669
Chicago Amani,gelmez metin yusuf,Tahrali Ilhan,Aydogan Muzeyyen,DENİZ Günnur,Cinar Suzan The Evaluation of Multidrug Resistance-Related Protein 1 as a Prognostic Factor in the Pediatric B-cell Acute Lymphoblastic Leukemia: A Pilot Study. (2022): 691 - 697. 10.14235/bas.galenos.2021.6669
MLA Amani,gelmez metin yusuf,Tahrali Ilhan,Aydogan Muzeyyen,DENİZ Günnur,Cinar Suzan The Evaluation of Multidrug Resistance-Related Protein 1 as a Prognostic Factor in the Pediatric B-cell Acute Lymphoblastic Leukemia: A Pilot Study. , 2022, ss.691 - 697. 10.14235/bas.galenos.2021.6669
AMA A,gelmez m,Tahrali I,Aydogan M,DENİZ G,Cinar S The Evaluation of Multidrug Resistance-Related Protein 1 as a Prognostic Factor in the Pediatric B-cell Acute Lymphoblastic Leukemia: A Pilot Study. . 2022; 691 - 697. 10.14235/bas.galenos.2021.6669
Vancouver A,gelmez m,Tahrali I,Aydogan M,DENİZ G,Cinar S The Evaluation of Multidrug Resistance-Related Protein 1 as a Prognostic Factor in the Pediatric B-cell Acute Lymphoblastic Leukemia: A Pilot Study. . 2022; 691 - 697. 10.14235/bas.galenos.2021.6669
IEEE A,gelmez m,Tahrali I,Aydogan M,DENİZ G,Cinar S "The Evaluation of Multidrug Resistance-Related Protein 1 as a Prognostic Factor in the Pediatric B-cell Acute Lymphoblastic Leukemia: A Pilot Study." , ss.691 - 697, 2022. 10.14235/bas.galenos.2021.6669
ISNAD , Amani vd. "The Evaluation of Multidrug Resistance-Related Protein 1 as a Prognostic Factor in the Pediatric B-cell Acute Lymphoblastic Leukemia: A Pilot Study". (2022), 691-697. https://doi.org/10.14235/bas.galenos.2021.6669
APA A, gelmez m, Tahrali I, Aydogan M, DENİZ G, Cinar S (2022). The Evaluation of Multidrug Resistance-Related Protein 1 as a Prognostic Factor in the Pediatric B-cell Acute Lymphoblastic Leukemia: A Pilot Study. Bezmiâlem Science, 10(6), 691 - 697. 10.14235/bas.galenos.2021.6669
Chicago Amani,gelmez metin yusuf,Tahrali Ilhan,Aydogan Muzeyyen,DENİZ Günnur,Cinar Suzan The Evaluation of Multidrug Resistance-Related Protein 1 as a Prognostic Factor in the Pediatric B-cell Acute Lymphoblastic Leukemia: A Pilot Study. Bezmiâlem Science 10, no.6 (2022): 691 - 697. 10.14235/bas.galenos.2021.6669
MLA Amani,gelmez metin yusuf,Tahrali Ilhan,Aydogan Muzeyyen,DENİZ Günnur,Cinar Suzan The Evaluation of Multidrug Resistance-Related Protein 1 as a Prognostic Factor in the Pediatric B-cell Acute Lymphoblastic Leukemia: A Pilot Study. Bezmiâlem Science, vol.10, no.6, 2022, ss.691 - 697. 10.14235/bas.galenos.2021.6669
AMA A,gelmez m,Tahrali I,Aydogan M,DENİZ G,Cinar S The Evaluation of Multidrug Resistance-Related Protein 1 as a Prognostic Factor in the Pediatric B-cell Acute Lymphoblastic Leukemia: A Pilot Study. Bezmiâlem Science. 2022; 10(6): 691 - 697. 10.14235/bas.galenos.2021.6669
Vancouver A,gelmez m,Tahrali I,Aydogan M,DENİZ G,Cinar S The Evaluation of Multidrug Resistance-Related Protein 1 as a Prognostic Factor in the Pediatric B-cell Acute Lymphoblastic Leukemia: A Pilot Study. Bezmiâlem Science. 2022; 10(6): 691 - 697. 10.14235/bas.galenos.2021.6669
IEEE A,gelmez m,Tahrali I,Aydogan M,DENİZ G,Cinar S "The Evaluation of Multidrug Resistance-Related Protein 1 as a Prognostic Factor in the Pediatric B-cell Acute Lymphoblastic Leukemia: A Pilot Study." Bezmiâlem Science, 10, ss.691 - 697, 2022. 10.14235/bas.galenos.2021.6669
ISNAD , Amani vd. "The Evaluation of Multidrug Resistance-Related Protein 1 as a Prognostic Factor in the Pediatric B-cell Acute Lymphoblastic Leukemia: A Pilot Study". Bezmiâlem Science 10/6 (2022), 691-697. https://doi.org/10.14235/bas.galenos.2021.6669