PURPOSE: Patients with acute lymphoblastic leukemia (ALL) are treated with a variety of chemotherapeutic drugs, which can be transported by six multidrug resistance-associated proteins (MRP). These MRPs have strongly overlapping functional activities. The aim of this study was to investigate the expression levels of MRP1 to MRP6 and study their effect on prognosis. EXPERIMENTAL DESIGN: The mRNA expression levels of MRP1 to MRP6 were analyzed by quantitative real-time PCR in leukemic blasts of 105 de novo ALL patients (adults, n=49; children, n=56) including 70% B-lineage and 30% T-lineage ALL patients. RESULTS: Adults showed a higher expressions of MRP1 (P=0.008), MRP2 (P=0.026), and MRP3 (P=0.039) than children. Interestingly, this difference disappeared when patients were categorized based on clinical outcome. Relapsed patients showed a higher expression of all MRP genes, except MRP4. For the total group of ALL patients, the expressions of MRP1, MRP2, MRP3, MRP5, and MRP6 predicted relapse. Moreover, high expression of all MRP genes, except MRP4, was associated with a reduced relapse-free survival in children and adults (MRP1, P=0.005; MRP2, P=0.008; MRP3, P=0.001; MRP5, P=0.016; MRP6, P=0.037). CONCLUSIONS: The present study shows that a subset of ALL patients with high MRP expression has an unfavorable prognosis independently of age.
PURPOSE:Patients with acute lymphoblastic leukemia (ALL) are treated with a variety of chemotherapeutic drugs, which can be transported by six multidrug resistance-associated proteins (MRP). These MRPs have strongly overlapping functional activities. The aim of this study was to investigate the expression levels of MRP1 to MRP6 and study their effect on prognosis. EXPERIMENTAL DESIGN: The mRNA expression levels of MRP1 to MRP6 were analyzed by quantitative real-time PCR in leukemic blasts of 105 de novo ALL patients (adults, n=49; children, n=56) including 70% B-lineage and 30% T-lineage ALL patients. RESULTS: Adults showed a higher expressions of MRP1 (P=0.008), MRP2 (P=0.026), and MRP3 (P=0.039) than children. Interestingly, this difference disappeared when patients were categorized based on clinical outcome. Relapsed patients showed a higher expression of all MRP genes, except MRP4. For the total group of ALL patients, the expressions of MRP1, MRP2, MRP3, MRP5, and MRP6 predicted relapse. Moreover, high expression of all MRP genes, except MRP4, was associated with a reduced relapse-free survival in children and adults (MRP1, P=0.005; MRP2, P=0.008; MRP3, P=0.001; MRP5, P=0.016; MRP6, P=0.037). CONCLUSIONS: The present study shows that a subset of ALL patients with high MRP expression has an unfavorable prognosis independently of age.
Authors: Jan Styczynski; Mariusz Wysocki; Robert Debski; Krzysztof Czyzewski; Beata Kolodziej; Beata Rafinska; Malgorzata Kubicka; Sylwia Koltan; Andrzej Koltan; Monika Pogorzala; Andrzej Kurylak; Dorota Olszewska-Slonina; Walentyna Balwierz; Edyta Juraszewska; Maria Wieczorek; Igor Olejnik; Maryna Krawczuk-Rybak; Marta Kuzmicz; Jerzy Kowalczyk; Jolanta Stefaniak; Wanda Badowska; Danuta Sonta-Jakimczyk; Tomasz Szczepanski; Michal Matysiak; Iwona Malinowska; Elzbieta Stanczak; Jacek Wachowiak; Benigna Konatkowska; Lidia Gil; Anna Balcerska; Lucyna Maciejka-Kapuscinska Journal: J Cancer Res Clin Oncol Date: 2007-08-02 Impact factor: 4.553
Authors: Jessica A Shafer; Conrad R Cruz; Ann M Leen; Stephanie Ku; An Lu; Alexandra Rousseau; Helen E Heslop; Cliona M Rooney; Catherine M Bollard; Aaron E Foster Journal: Leuk Lymphoma Date: 2010-05
Authors: Xing-Xiang Peng; Zhi Shi; Amit K Tiwari; Vijaya L Damaraju; Liwu Fu; Carol E Cass; Charles R Ashby; Gary D Kruh; Zhe-Sheng Chen Journal: Oncol Lett Date: 2011-03-21 Impact factor: 2.967