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 lymp hoblastic leukemia (ALL), Studies suggest an association with a good progno sis; however, relapse can occur. We studied the relation between t(12;21), determined by fluorescence in situ hybridization or polymerase chain reacti on, 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 predniso lone, dexamethasone, daunorubicin, thiopurines, epipodophyllotoxins, and 4- HOO-ifosfamide. However, the TEL/AML1-positive patients were relatively mor e sensitive to L-asparaginase (ASP; 5.9-fold; P = .029) and slightly but si gnificantly more resistant to vincristine (1.5-fold; P = .011) and cytarabi ne (1.5-fold; P = .014), After matching for unevenly distributed patient ch aracteristics-that is, excluding patients younger than 12 months, patients with CD10-negative immature B-lineage ALL, patients with Philadelphia chrom osome, and patients who were hyperdiploid (more than 50 chromosomes) from t he TEL/AML1 negative group-the only remaining difference was a relative sen sitivity 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 sensit ivity, except for ASP, indicating that these patients could benefit from tr eatment schedules with significant use of this drug. (C) 2000 by The Americ an Society of Hematology.