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

N. L. Ramakers-Van Woerden, R. Pieters, A. H. Loonen, I. Hubeek, E. Van Drunen, H. Bema Beverloo, R. M. Slater, J. Harbott, J. Seyfarth, E. R. Van Wering, K. Hahlen, K. Schmiegelow, G. E. Janka-Schaub, A. J.P. Veerman

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127 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)1094-1099
Aantal pagina's6
TijdschriftBlood
Volume96
Nummer van het tijdschrift3
StatusGepubliceerd - 1 aug. 2000
Extern gepubliceerdJa

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