In vitro drug resistance profile of Philadelphia positive acute lymphoblastic leukemia is heterogeneous and related to age: A report of the Dutch and German Leukemia Study Groups
✍ Scribed by Woerden, N.L. Ramakers-van ;Pieters, R. ;Hoelzer, D. ;Slater, R.M. ;den Boer, M.L. ;Loonen, A.H. ;Harbott, J. ;Janka-Schaub, G.E. ;Ludwig, W-D ;Ossenkoppele, G.J. ;van Wering, E.R. ;Veerman, A.J.P.
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 123 KB
- Volume
- 38
- Category
- Article
- ISSN
- 0098-1532
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✦ Synopsis
Abstract
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‐0positive (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. Med Pediatr Oncol 2002;38:379–386. © 2002 Wiley‐Liss, Inc.