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.