Yıl: 2012 Cilt: 29 Sayı: 2 Sayfa Aralığı: 120 - 125 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

The frequency and clinical relevance of multidrug resistance protein expression in patients with lymphoma

Öz:
Amaç: Çoklu ilaç direnci malign lenfomalarda tedavi başarısızlığının nedenlerindendir. Fakat çoklu ilaç direnci proteinlerinin sıklığı ve klinik önemiyle ilgili çelişkiler mevcuttur. Biz bu çalışmada lenfomalı hastalarımızda en sık görülen çoklu ilaç direnci proteinlerinin ifadelerini araştırdık. Gereç ve Yöntemler: Çalışmaya daha önce tedavi almamış 44 hasta (21 non Hodgkin lenfoma, 13 malign olmayan lenfadenopati, 10 Hodgkin lenfoma) alındı. MDR1, MRP ve LRP ifadeleri lenf nodu biyopsi örneklerinde kantitatif PCR ile değerlendirildi. Bulgular: Non Hodgkin lenfomada MDR1 %23.8 (5/21), MRP %57.14 (12/21), LRP %90.47 (19/21) pozitifti. Malign olmayan lenfadenopatili hastalarda MDR1 %46.15 (6/13), MRP %84.61 (11/13), LRP %100 (13/13) pozitifti. Hodgkin lenfomada MDR1 %50 (5/10), MRP %50 (5/10), LRP %80 (8/10) pozitifti. MDR1, MRP ve LRP ifadeleri 3 grup arasında farklı değildi. İfadeler tümör evresi, eritrosit sedimantasyon hızı, C reaktif protein, beta 2 mikroglobulin, ilk sıra tedaviye yanıt, serum laktat dehidrogenaz ve albumin düzeyiyle ilişkili değildi. MDR1 ve MRP pozitif ve negatif hastaların yaşam süreleri arasında da fark bulamadık (LRP pozitif ve negatif hastalar arası karşılaştırma yapmak az hasta sayısı nedeniyle mümkün olmadı). Sonuç: Verilerimize göre, bu grup hastalardaki tedavi başarısızlığını aydınlatmak için gelecekte yapılacak çalışmalar çoklu ilaç direncinin alternatif yolaklarına yönlendirilebilir.
Anahtar Kelime:

Konular: Hematoloji

Çoklu ilaç direnci protein ifadelerinin lenfomalardaki sıklık ve klinik önemi

Öz:
Objective: Multidrug resistance is a cause of treatment failure in patients with malignant lymphoma; however, the frequency and clinical relevance of multidrug resistance protein expression are unclear. The present study aimed to investigate expression of the most common multidrug resistance proteins in a group of lymphoma patients. Material and Methods: The study included 44 previously untreated lymphoma patients (non-Hodgkin’s lymphoma [n = 21], non-malignant lymphadenopathy [n = 13], and Hodgkin’s lymphoma [n = 10]). MDR1, MRP, and LRP expression was assessed via quantitative PCR of lymph node biopsy specimens. Results: In the non-Hodgkin’s lymphoma group MDR1 was positive in 23.8% (5/21) of the patients, MRP was positive in 57.14% (12/21), and LRP was positive in 90.47% (19/21). In the non-malignant lymphadenopathy group, MDR1 was positive in 46.15% (6/13) of the patients, MRP was positive in 84.61% (11/13), and LRP was positive in 100% (13/13). In the Hodgkin’s lymphoma group MDR1 was positive in 50% (5/10) of the patients, MRP was positive in 50% (5/10), and LRP was positive in 80% (8/10). MDR1, MRP, and LRP expression did not differ between the 3 groups. Furthermore, MDR1, MRP, and LRP expression wasn’t associated with tumor stage, response to first-line therapy, the erythrocyte sedimentation rate, or C reactive protein, beta 2 microglobulin, serum lactate dehydrogenase, and albumin levels. Additionally, survival time in the MDR1- and MRP-positive, and MDR1- and MRP-negative patients did not differ (comparison of LRP was not possible due to the small number of LRP-negative patients). Conclusion: According to the present findings, future studies should investigate alternative pathways of multidrug resistance in order to arrive at a better understanding of treatment failure in lymphoma patients.
Anahtar Kelime:

Konular: Hematoloji
Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Biedler JL, Riehm H. Cellular resistance to actinomycin D in Chinese hamster cells in vitro: cross-resistance, radioautographic and cytogenetic studies. Cancer Res 1970; 30: 1174-1184.
  • 2. Borst P, Elferink RO. Mammalian ABC transporteri in health and disease. Annu Rev Biochem 2002; 71: 537-592.
  • 3. Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: a role of ATP dependent transporters. Nat Rev Cancer 2002; 2: 48-58.
  • 4. Ross DD. Novel mechanisms of drug resistance in leukemia. Leukemia 2000;14: 467-473.
  • 5. Cho EY, Gong G, Khang SK, Kang YK, Huh J. Fine needle aspiration cytology of CD56-positive natural killer/T-cell lymphoma of soft tissue. Cancer 2002; 96: 344-350.
  • 6. Shen DW, Cardarelli C, Hwang J, Cornwell M, Richert N, Ishii S, Pastan I, Gottesman MM. Multiple drug-resistant human KB carcinoma cells independently selected for high- level resistance to colchicine, adriamycin or vinblastine show changes in expression of specific proteins. J Biol Chem 1986; 261: 7762-7770.
  • 7. Kruh GD, Chan A, Myers K, Gaughan K, Miki T, Aaronson SA. Expression complementary DNA library transfer establishes mrp as a multidrug resistance gene. Cancer Res 1994; 54: 1649-1652.
  • 8. Scheper RJ, Broxterman HJ, Scheffer GL, Kaaijk P, Dalton WS, van Heijningen TH, van Kalken CK, Slovak ML, de Vries EG, van der Valk P, J.L.M. Meijer C, HM Pinedo. Overexpression of a M(r) 110,000 vesicular protein in non- P-glycoprotein- mediated multidrug resistance. Cancer Res 1993; 53: 1475-1479.
  • 9. Kang YK, Zhan Z, Regis J, Alvarez M, Robey R, Meadows B, Dickstein B, Lee JS, Otsuki T, Stetler-Stevenson M, Jaffe ES, Solomon D, Wilson WH, Fojo A, Bates ES. Expression of mdr-1 in refractory lymphoma: quantitation by polymerase chain reaction and validation of assay. Blood 1995; 86: 1515-1524.
  • 10. Cole SP, Bhardjaw G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AM, Deeley RG. Overexpression of a transporter gene in a multidrug- resistant human lung cancer cell line. Science 1992; 258: 1650-1654.
  • 11. 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.
  • 12. Filipits M, Drach J, Pohl G, Schuster J, Stranzl T, Ackermann J, Königsberg R, Kaufmann H, Gisslinger H, Huber H, Ludwig H, Pirker R. Expression of the lung resistance protein predicts poor outcome in patients with multiple myeloma. Clin Cancer Res 1999; 5: 2426-2430.
  • 13. 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.
  • 14. Borg AG, Burgess R, Green LM, Scheper RJ, Yin JA. Overexpression of lung-resistance protein and increased P-glycoprotein function in acute myeloid leukemia cells predict a poor response to chemotherapy and reduced patient survival. Br J Haematol 1998; 103: 1083-1091.
  • 15. Yasunami T, Wang Y, Tsuji K, Takanashi M, Yamada Y, Motoji T. Multidrug resistance protein expression of adult T-cell leukemia/lymphoma. Leuk Res 2007; 31: 465-470.
  • 16. Yuen AR, Sikic BI. Multidrug resistance in lymphomas. J Clin Oncol 1994; 12: 2453-2459.
  • 17. Marie JP. P-glycoprotein in adult hematologic malignancies. Hematol Oncol Clin North Am 1995; 9: 239-249.
  • 18. Sandor V, Wilson W, Fojo T, Bates SE. The role of MDR-1 in refractory lymphoma. Leuk Lymph 1997; 28: 23-31.
  • 19. Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an International Workshop to standardize response criteria for non-Hodgkin’s lymphomas. J Clin Oncol 1999; 17: 1244-1253.
  • 20. Saglam A, Hayran M, Uner AH. Immunohistochemical expression of multidrug resistance proteins in mature T/NK cell lymphomas. APMIS 2008; 116: 791-800.
  • 21. Liu Q, Ohshima K, Kikuchi M. High expression of MDR-1 gene and P-glycoprotein in initial and re-biopsy specimens of relapsed B cell lymphoma. Histopathology 2001; 38: 209-216.
  • 22. Pileri SA, Sabattini E, Falini B, Tazzari PL, Gherlinzoni F, Michieli MG, Damiani D, Zucchini L, Gobbi M, Tsuruo T. Immunohistochemical detection of multidrug transport protein P170 in human normal tissues and malignant lymphomas. Histopathology 1991; 19: 131-140.
  • 23. Cheng AL, Su IJ, Chen YC, Lee TC, Wang CH. Expression of P-glycoprotein and anionic glutathione S-transferase in recurrent lymphomas: the possible role of Ebstein Barr virus immunophenotypes and other predisposing factors. J Clin Oncol 1993; 11: 109-115.
  • 24. Niehans GA, Jaszcz W, Brunetto V, Perri RT, Gajl-Peczalska K, Wick MR, Tsuruo T, Bloomfield CD. Immunohistochemical identification of P-glycoprotein in previously untreated diffuse large cell and immunoblastic lymphomas. Cancer Res 1992; 52: 3768-3775.
  • 25. Rodriguez C, Commes T, Robert J, Rossi JF. Expression of P-glycoprotein and anionic glutathione S-transferase genes in non Hodgkin’s lymphomas. Leuk Res 1993; 17: 149-156.
  • 26. Miller TP, Grogan TM, Dalton WS, Spier CM, Scheper RJ, Salmon SE. P-glycoprotein expression in malignant lymphoma and reversal of clinical drug resistance with chemotherapy plus high dose verapamil. J Clin Oncol 1991; 9: 17-24.
  • 27. Goldstein LJ, Galski H, Fojo A, Willingham M, Lai SL, Gazdar A, Pirker R, Green A, Crist W, Brodeur GM. Expression of a multidrug resistance gene in human cancers. J Natl Cancer Inst 1989; 81: 116-124.
  • 28. Filipits M, Jaeger U, Simonitsch I, Chizzali-Bonfadin C, Heinzl H, Pirker R. Clinical relevance of the lung resistance protein in diffuse large B cell lymphomas. Clin Cancer Res 2000; 6: 3417-3423.
  • 29. Filipits M, Stranzl T, Pohl G, Heinzl H, Jäger U, Geissler K, Fonatsch C, Haas OA, Lechner K, Pirker R. Drug resistance factors in acute myeloid leukemia: a comperative analysis. Leukemia 2000; 14: 68-76.
  • 30. den Boer ML, Pieters R, Kazemier KM, Rottier MM, Zwaan CM, Kaspers GJ, Janka-Schaub G, Henze G, Creutzig U, Scheper RJ, Veerman AJ. Relationship between major vault protein/lung resistance protein, multidrug resistance- associated protein, P-glycoprotein expression and drug resistance in childhood leukemia. Blood 1998; 91: 2092- 2098.
  • 31. Ohsawa M, Ikura Y, Fukushima H, Shirai N, Sugama Y, Suekane T, Hirayama M, Hino M, Ueda M. Immunohistochemical expression of multidrug resistance proteins as a predictor of poor response to chemotherapy and prognosis in patients with nodal diffuse large B cell lymphoma. Oncology 2005; 68: 422-431.
  • 32. Huang WT, Huang CC, Weng SW, Eng HL. Expression of the multidrug resistance protein MRP and the lung resistance protein LRP in nasal NK/T cell lymphoma: further exploring the role of P53 and WT1 gene. Pathology 2009; 41: 127-132.
  • 33. Li L, Su LP, Ma L, Zhao J, Zhu L, Zhou YA. Expression and significance of P-gp/mdr1 mRNA, MRP and LRP in non- Hodgkin’s lymphoma. Zhonghua Zhong Liu Za Zhi 2009; 31: 199-202.
  • 34. Zhan Z, Sandor VA, Gamelin E, Regis J, Dickstein B, Wilson W, Fojo AT, Bates SE. Expression of multidrug resistance associated protein gene in refractory lymphoma: quantitation by a validated polymerase chain reaction assay. Blood 1997; 89: 3795-3800.
  • 35. Coiffier B. Monoclonal antibody as therapy for malignant lymphomas. C R Biol 2006; 329:241-254.
  • 36. Ghetie MA, Marches R, Kufert S, Vitetta ES. An anti-CD19 antibody inhibits the interaction between P-gp and CD19, causes P-gp to translocate out of lipid rafts and chemosensitizes a MDR lymphoma cell line. Blood 2004; 104:178-183.
  • 37. Klimecki WT, Futscher BW, Grogan TM, Dalton WS. P-glycoprotein expression and function in circulating blood cells from normal volunteers. Blood 1994; 83:2451-2458.
APA GÜNDÜZ E, DİNCER M, YILDIZ G, BAL C, GULBAS Z (2012). The frequency and clinical relevance of multidrug resistance protein expression in patients with lymphoma. , 120 - 125.
Chicago GÜNDÜZ Eren,DİNCER MURAT,YILDIZ Güniz,BAL CENGIZ,GULBAS ZAFER The frequency and clinical relevance of multidrug resistance protein expression in patients with lymphoma. (2012): 120 - 125.
MLA GÜNDÜZ Eren,DİNCER MURAT,YILDIZ Güniz,BAL CENGIZ,GULBAS ZAFER The frequency and clinical relevance of multidrug resistance protein expression in patients with lymphoma. , 2012, ss.120 - 125.
AMA GÜNDÜZ E,DİNCER M,YILDIZ G,BAL C,GULBAS Z The frequency and clinical relevance of multidrug resistance protein expression in patients with lymphoma. . 2012; 120 - 125.
Vancouver GÜNDÜZ E,DİNCER M,YILDIZ G,BAL C,GULBAS Z The frequency and clinical relevance of multidrug resistance protein expression in patients with lymphoma. . 2012; 120 - 125.
IEEE GÜNDÜZ E,DİNCER M,YILDIZ G,BAL C,GULBAS Z "The frequency and clinical relevance of multidrug resistance protein expression in patients with lymphoma." , ss.120 - 125, 2012.
ISNAD GÜNDÜZ, Eren vd. "The frequency and clinical relevance of multidrug resistance protein expression in patients with lymphoma". (2012), 120-125.
APA GÜNDÜZ E, DİNCER M, YILDIZ G, BAL C, GULBAS Z (2012). The frequency and clinical relevance of multidrug resistance protein expression in patients with lymphoma. Turkish Journal of Hematology, 29(2), 120 - 125.
Chicago GÜNDÜZ Eren,DİNCER MURAT,YILDIZ Güniz,BAL CENGIZ,GULBAS ZAFER The frequency and clinical relevance of multidrug resistance protein expression in patients with lymphoma. Turkish Journal of Hematology 29, no.2 (2012): 120 - 125.
MLA GÜNDÜZ Eren,DİNCER MURAT,YILDIZ Güniz,BAL CENGIZ,GULBAS ZAFER The frequency and clinical relevance of multidrug resistance protein expression in patients with lymphoma. Turkish Journal of Hematology, vol.29, no.2, 2012, ss.120 - 125.
AMA GÜNDÜZ E,DİNCER M,YILDIZ G,BAL C,GULBAS Z The frequency and clinical relevance of multidrug resistance protein expression in patients with lymphoma. Turkish Journal of Hematology. 2012; 29(2): 120 - 125.
Vancouver GÜNDÜZ E,DİNCER M,YILDIZ G,BAL C,GULBAS Z The frequency and clinical relevance of multidrug resistance protein expression in patients with lymphoma. Turkish Journal of Hematology. 2012; 29(2): 120 - 125.
IEEE GÜNDÜZ E,DİNCER M,YILDIZ G,BAL C,GULBAS Z "The frequency and clinical relevance of multidrug resistance protein expression in patients with lymphoma." Turkish Journal of Hematology, 29, ss.120 - 125, 2012.
ISNAD GÜNDÜZ, Eren vd. "The frequency and clinical relevance of multidrug resistance protein expression in patients with lymphoma". Turkish Journal of Hematology 29/2 (2012), 120-125.