TEL/AML1 gene fusion is related to in vitro drug sensitivity for L- asparaginase in childhood acute lymphoblastic leukemia

The t(12;21) translocation resulting in TEL/AML1 gene fusion is present in approximately 25% of patients with precursor B-lineage pediatric acute lymphoblastic leukemia (ALL). Studies suggest an association with a good prognosis; however, relapse can occur. We studied the relation between t(12;21), determined by fluorescence in situ hybridization or polymerase chain reaction, and in vitro drug resistance, measured by the MTT assay, in childhood B-lineage ALL at diagnosis. A total of 180 ALL samples were tested, 51 (28%) of which were positive for t(12;21). The median LC₅₀ values did not differ significantly between TEL/AML1-positive and -negative samples for prednisolone, dexamethasone, daunorubicin, thiopurines, epipodophyllotoxins, and 4-HOO-ifosfemide. However, the TEL/AML1-positive patients were relatively more sensitive to L-asparaginase (ASP; 5.9-fold; P = .029) and slightly but significantly more resistant to vincristine (1.5-fold; p = .011) and cytarabine (1.5-fold; p = .014). After matching for unevenly distributed patient characteristics - that is, excluding patients younger then 12 months, patients with cd10-negative immature B-lineage ALL, patients with Philadelphia chromosome, and patients who were hyperdiploid (more than 50 chromosomes) from the TEL/ AML1 negative group - the only remaining difference was a relative sensitivity for asp in the TEL/AML1-positive samples (10.8-fold; P = .012). In conclusion, the presence of TEL/AML1 gene fusion in childhood precursor B-lineage ALL does not seem to be associated with a high in vitro drug sensitivity, except for ASP, indicating that these patients could benefit from treatment schedules with significant use of this drug.(C) 2000 by The American Society of Hematology.