BACKGROUND: The t(9;22)(q34;q11) translocation leading to the Philadelphia (Ph) chromosome resulting in BCR-ABL gene fusion is associated with a poor prognosis in acute lymphoblastic leukemia (ALL). PROCEDURE: We studied the relation between t(9;22), determined by karyotype, fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR), and in vitro drug resistance, measured by the MTT assay, in precursor B-cell ALL at diagnosis. The findings in twenty-one Ph-positive (Ph+) childhood common/precursorB (c/preB) cases were compared with 254 Ph-negative (Ph-) ALL cases. RESULTS: A large range of LC(50) values was found within the Ph+ patients. Moreover, LC(50) values did not differ significantly between Ph+ and Ph- samples for prednisolone, dexamethasone, L-asparaginase, vincristine, anthracyclines, thiopurines, epipodophyllotoxins, and 4H00-ifosfamide, even after matching for important prognostic features (age, white blood cell count (WBC), and immunophenotype). Adult Ph+ (n = 12) ALL was more resistant to prednisolone (> 270-fold, P = 0.030), and displayed an overall tendency to resistance when compared to matched cases of Ph- (n = 15) adult precursor B-cell ALL. Within Ph+ ALL, in vitro prednisolone resistance increased significantly with age (P = 0.006). The expression of lung resistance protein (LRP), but not P-glycoprotein (P-gp) or multidrug resistance protein (MRP), was significantly higher in all Ph+ patients. CONCLUSIONS: Both childhood and adult Ph+ precursor B-cell ALL samples display a heterogeneous in vitro resistance profile, with relatively sensitive and resistant cases. The adult Ph+ samples, however, are generally more resistant compared to matched Ph- controls, reaching significance for prednisolone. The correlation of prednisolone resistance with age within the Ph+ cases might help explain the poorer prognosis of adult Ph+ ALL. Copyright 2002 Wiley-Liss, Inc.
BACKGROUND: The t(9;22)(q34;q11) translocation leading to the Philadelphia (Ph) chromosome resulting in BCR-ABL gene fusion is associated with a poor prognosis in acute lymphoblastic leukemia (ALL). PROCEDURE: We studied the relation between t(9;22), determined by karyotype, fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR), and in vitro drug resistance, measured by the MTT assay, in precursor B-cell ALL at diagnosis. The findings in twenty-one Ph-positive (Ph+) childhood common/precursorB (c/preB) cases were compared with 254 Ph-negative (Ph-) ALL cases. RESULTS: A large range of LC(50) values was found within the Ph+ patients. Moreover, LC(50) values did not differ significantly between Ph+ and Ph- samples for prednisolone, dexamethasone, L-asparaginase, vincristine, anthracyclines, thiopurines, epipodophyllotoxins, and 4H00-ifosfamide, even after matching for important prognostic features (age, white blood cell count (WBC), and immunophenotype). Adult Ph+ (n = 12) ALL was more resistant to prednisolone (> 270-fold, P = 0.030), and displayed an overall tendency to resistance when compared to matched cases of Ph- (n = 15) adult precursor B-cell ALL. Within Ph+ ALL, in vitro prednisolone resistance increased significantly with age (P = 0.006). The expression of lung resistance protein (LRP), but not P-glycoprotein (P-gp) or multidrug resistance protein (MRP), was significantly higher in all Ph+ patients. CONCLUSIONS: Both childhood and adult Ph+ precursor B-cell ALL samples display a heterogeneous in vitro resistance profile, with relatively sensitive and resistant cases. The adult Ph+ samples, however, are generally more resistant compared to matched Ph- controls, reaching significance for prednisolone. The correlation of prednisolone resistance with age within the Ph+ cases might help explain the poorer prognosis of adult Ph+ ALL. Copyright 2002 Wiley-Liss, Inc.
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: Michael A Dengler; Annette M Staiger; Matthias Gutekunst; Ute Hofmann; Malgorzata Doszczak; Peter Scheurich; Matthias Schwab; Walter E Aulitzky; Heiko van der Kuip Journal: PLoS One Date: 2011-09-20 Impact factor: 3.240