Establishment and characterization of an STI571-resistant human myelogenous leukemia cell line, SR-1.

Abstract

The tyrosine kinase inhibitor STI571 is an effective agent for the treatment of chronic myelogenous leukemia (CML). However, a lack of response to STI571 or the recurrence of the disease after a transient initial response is usually seen in patients with advanced stage CML. We have established a novel STI571 (Gleevec/Glivec, imatinib mesylate)-resistant acute myelocytic leukemia cell line (SR-1) from an STI571-resistant blast crisis patient. By flow cytometry, the immunophenotype of SR-1 was found to be compatible with a myeloid lineage (CD13+, CD33+, HLA-DR+, anti-MPO+). Conventional cytogenetics showed a three-way reciprocal translocation involving 7p22, 9q34, and 22q11.2, i.e., a variant Philadelphia chromosome translocation. The BCR/ABL rearrangement was detected by fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction. To determine the tumorigenicity of the SR-1 cell line in vivo, cells were injected subcutaneously into severe combined immunodeficiency mice. Four weeks later, tumors had grown and showed the same laboratory findings as in SR-1. Although STI571 resistance is a known treatment complication, in vivo STI571-resistant cell lines have not been fully established. We hope that our SR-1 cell line may be useful in molecular pathogenetic investigations of STI571-resistant CML.