Expressão do gene MRP1 em leucemias agudas

Autores

  • Frouzandeh Mahjoubi National Institute of Genetic Engineering and Biotechnology and University of Tehran
  • Masoud Golalipour National Institute of Genetic Engineering and Biotechnology and University of Tehran
  • Ardeshir Ghavamzadeh National Institute of Genetic Engineering and Biotechnology and University of Tehran
  • Kamran Alimoghaddam National Institute of Genetic Engineering and Biotechnology and University of Tehran

Palavras-chave:

Resistência a múltiplas drogas, Quimioterapia, Reação em cadeia da polimerase via transcriptase reversa, Leucemia mielóide, Leucemia linfocítica aguda

Resumo

CONTEXTO E OBJETIVO: A superexpressão do gene de resistência a múltiplas drogas associado à proteína 1 (MRP1) tem sido ligada à resistência à quimioterapia in vitro, porém pouco é conhecido sobre seu impacto clínico nos pacientes com leucemia aguda. Nosso objetivo foi investigar a possível associação entre a expressão do gene MRP1 e os desfechos clínicos em pacientes iranianos com leucemia. DESENHO E LOCAL: Este foi um estudo analítico transversal em pacientes encaminhados ao Centro de Pesquisa em Hematologia, Oncologia e Células Tronco do Hospital Público de Sharyatee, com diagnóstico de leucemia mielóide aguda (LMA) ou leucemia linfoblástica aguda (LLA). Todo trabalho molecular foi realizado no NIGEB (instituição pública). MÉTODOS: Para correlação de marcadores prognósticos e desfechos clínicos da leucemia aguda, a expressão do MRP1 foi avaliada em 35 casos de LMA e 17 de LLA, usando a reação da cadeia de polimerase quantitativa em tempo real, e comparando este dado ao tipo de resposta à quimioterapia. RESULTADOS: A média da expressão em pacientes com LMA em remissão completa (0,032 ± 0,031) foi significativamente menor que aquela dos casos recidivantes (0,422 ± 0,297). Por outro lado, não foram observadas diferenças significativas nos níveis de mRNA para MRP1 entre os casos de LLA com remissão completa e os casos recidivantes. Houve uma diferença na expressão de MRP1 entre pacientes com prognóstico citogenético não-favorável e favorável (0,670 ± 0,074 e 0,028 ± 0,013, respectivamente). A expressão de MRP1 em M5 foi significativamente maior (valor de p = 0,001) do que em outros subtipos. CONCLUSÕES: Os achados sugerem que a alta expressão de MRP1 se associou com o pior desfecho clínico, estando correlacionada com o subtipo M5 e os subgrupos citogenéticos menos favoráveis para os pacientes com LMA, mas não para pacientes com LLA.

Downloads

Não há dados estatísticos.

Biografia do Autor

Frouzandeh Mahjoubi, National Institute of Genetic Engineering and Biotechnology and University of Tehran

PhD. Project leader and supervisor of Masoud Golalipour, Department of Clinical Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.

Masoud Golalipour, National Institute of Genetic Engineering and Biotechnology and University of Tehran

PhD. PhD student who performed all the laboratory work, Department of Clinical Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.

Ardeshir Ghavamzadeh, National Institute of Genetic Engineering and Biotechnology and University of Tehran

MD. Hematology, Oncology and Stem Cell Research Center, Medical Sciences, University of Tehran, Tehran, Iran.

Kamran Alimoghaddam, National Institute of Genetic Engineering and Biotechnology and University of Tehran

MD. Hematology, Oncology and Stem Cell Research Center, Medical Sciences, University of Tehran, Tehran, Iran.

Referências

Sonneveld P. Multidrug resistance in haematological malignan- cies. J Intern Med. 2000;247(5):521-34.

Büchner T. Treatment of adult acute leukemia. Curr Opin Oncol. 1997;9(1):18-25.

Marie JP, Zhou DC, Gurbuxani S, Legrand O, Zittoun R. MDR1/P-glycoprotein in haematological neoplasms. Eur J Cancer. 1996;32A(6):1034-8.

Cole SP, Bhardwaj G, Gerlach JH, et al. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science. 1992;258(5088):1650-4.

Grant CE, Valdimarsson G, Hipfner DR, Almquist KC, Cole SP, Deeley RG. Overexpression of multidrug resistance-associated protein (MRP) increases resistance to natural product drugs. Cancer Res. 1994;54(2):357-61.

Legrand O, Perrot JY, Simonin G, Baudard M, Marie JP. JC-1: a very sensitive fluorescent probe to test Pgp activity in adult acute myeloid leukemia. Blood. 2001;97(2):502-8.

Solary E, Drenou B, Campos L, et al. Quinine as a multi- drug resistance inhibitor: a phase 3 multicentric randomized study in adult de novo acute myelogenous leukemia. Blood. 2003;102(4):1202-10.

Broxterman HJ, Sonneveld P, Pieters R, et al. Do P-glycoprotein and major vault protein (MVP/LRP) expression correlate with in vitro daunorubicin resistance in acute myeloid leukemia? Leukemia. 1999;13(2):258-65.

Wuchter C, Leonid K, Ruppert V, et al. Clinical significance of P-glycoprotein expression and function for response to induction chemotherapy, relapse rate and overall survival in acute leukemia. Haematologica. 2000;85(7):711-21.

Marbeuf-Gueye C, Broxterman HJ, Dubru F, Priebe W, Garnier-Suillerot A. Kinetics of anthracycline efflux from multidrug resistance protein-expressing cancer cells compared with P-glycoprotein-expressing cancer cells. Mol Pharmacol. 1998;53(1):141-7.

Legrand O, Zittoun R, Marie JP. Role of MRP1 in mul- tidrug resistance in acute myeloid leukemia. Leukemia. 1999;13(4):578-84.

Cole SP, Deeley RG. Multidrug resistance mediated by the ATP-binding cassette transporter protein MRP. Bioessays. 1998;20(11):931-40.

Lockhart AC, Tirona RG, Kim RB. Pharmacogenetics of ATP- binding cassette transporters in cancer and chemotherapy. Mol Cancer Ther. 2003;2(7):685-98.

Beck WT, Grogan TM. Methods to detect P-glycoprotein and implications for other drug resistance-associated proteins. Leukemia. 1997;11(7):1107-9.

Beck WT, Grogan TM, Willman CL, et al. Methods to detect P-glycoprotein-associated multidrug resistance in patients’ tumors: consensus recommendations. Cancer Res. 1996;56(13):3010-20.

Ohno N, Tani A, Chen ZS, et al. Prognostic significance of multidrug resistance protein in adult T-cell leukemia. Clin Cancer Res. 2001;7(10):3120-6.

Plasschaert SL, Vellenga E, de Bont ES, et al. High functional P-glycoprotein activity is more often present in T-cell acute lymphoblastic leukaemic cells in adults than in children. Leuk Lymphoma. 2003;44(1):85-95.

Michieli M, Damiani D, Ermacora A, et al. P-glycoprotein, lung resistance-related protein and multidrug resistance associated protein in de novo acute non-lymphocytic leukaemias: biological and clinical implications. Br J Haematol. 1999;104(2):328-35.

Mitelman F. ISCN 1995. An international system for human cytogenetic nomenclature. Basel: Karger; 1995.

Mitelman F. ISCN 1991. Guidelines for cancer cytogenetics: supplement to an international system for human cytogenetic nomenclature. Basel: Karger; 1991.

Bailly JD, Muller C, Jaffrézou JP, et al. Lack of correlation between expression and function of P-glycoprotein in acute myeloid leukemia cells lines. Leukemia. 1995;9(5):799-807.

Zhou DC, Zittoun R, Marie JP. Expression of multidrug resistance-associated protein (MRP) and multidrug resis- tance (MDR1) genes in acute myeloid leukemia. Leukemia. 1995;9(10):1661-6.

Fujimaki S, Funato T, Harigae H, et al. Quantitative analysis of a MDR1 transcript for prediction of drug resistance in acute leukemia. Clin Chem. 2002;48(6 Pt 1):811-7.

Filipits M, Suchomel RW, Zöchbauer S, Brunner R, Lechner K, Pirker R. Multidrug resistance-associated protein in acute myeloid leukemia: No impact on treatment outcome. Clin Cancer Res. 1997;3(8):1419-25.

den Boer ML, Pieters R, Kazemier KM, et al. Relationship between major vault protein/lung resistance protein, multidrug resistance-associated protein, P-glycoprotein expression, and drug resistance in childhood leukemia. Blood. 1998:91(6):2092-8.

van der Kolk DM, de Vries EG, Noordhoek L, et al. Activity and expression of the multidrug resistance proteins P-glycoprotein, MRP1, MRP2, MRP3 and MRP5 in de novo and relapsed acute myeloid leukemia. Leukemia. 2001;15(10):1544-53.

Steinbach D, Friedrich J, Dawczynski K, et al. Are MTT assays the right tool to analyze drug resistance caused by ABC-transporters in patient samples? Leuk Lymphoma. 2005;46(9):1357-63.

Yague E, Armesilla AL, Harrison G, et al. P-glycoprotein (MDR1) expression in leukemic cells is regulated at two distinct steps, mRNA stabilization and translational initiation. J Biol Chem. 2003;278(12):10344-52.

Manohar CF, Bray JA, Salwen HR, et al. MYCN-mediated regulation of the MRP1 promoter in human neuroblastoma. Oncogene. 2004;23(3):753-62.

Zhu G, Chang Y, Zuo J, et al. Fudenine, a C-terminal truncated rat homologue of mouse prominin, is blood glucose-regulated and can up-regulate the expression of GAPDH. Biochem Bio- phys Res Commun. 2001;281(4):951-6.

Goidin D, Mamessier A, Staquet MJ, Schmitt D, Berthier- Vergnes O. Ribosomal 18S RNA prevails over glyceraldehyde- 3-phosphate dehydrogenase and beta-actin genes as internal standard for quantitative comparison of mRNA levels in invasive and noninvasive human melanoma cell subpopulations. Anal Biochem. 2001;295(1):17-21.

Oselin K, Mrozikiewicz PM, Pähkla R, Roots I. Quantitative determination of the human MRP1 and MRP2 mRNA expres- sion in FACS-sorted peripheral blood CD4+, CD8+, CD19+, and CD56+ cells. Eur J Haematol. 2003;71(2):119-23.

Kuss BJ, Deeley RG, Cole SP, et al. Deletion of gene for multidrug resistance in acute myeloid leukemia with inver- sion in chromosome 16: prognostic implications. Lancet. 1994;343(8912):1531-4.

Leith CP, Kopecky KJ, Chen IM, et al. Frequency and clini- cal significance of the expression of the multidrug resistance proteins MDR1/P-glycoprotein, MRP1, and LRP in acute myeloid leukemia: a Southwest Oncology Group Study. Blood. 1999;94(3):1086-99.

Downloads

Publicado

2008-05-05

Como Citar

1.
Mahjoubi F, Golalipour M, Ghavamzadeh A, Alimoghaddam K. Expressão do gene MRP1 em leucemias agudas. Sao Paulo Med J [Internet]. 5º de maio de 2008 [citado 14º de março de 2025];126(3):172-9. Disponível em: https://periodicosapm.emnuvens.com.br/spmj/article/view/1977

Edição

v. 126 n. 3 (2008)

Seção

Artigo Original

Licença

Creative Commons License
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.