Establishment and characterization of an STI571-resistant human myelogenous leukemia cell line, SR-1.
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.
Kwon
Hyuk-Chan
HC
Department of Internal Medicine, Dong-A University College of Medicine, 3-1 Dongdaeshindong, Seo-Ku, Busan, 601-715, Korea.
Kim
Sung-Hyun
SH
Kim
Jae-Seok
JS
Han
Hoon
H
Roh
Mee Sook
MS
Han
Jin-Yeong
JY
Seo
Su-Yeong
SY
Lee
Young-Ho
YH
Kim
Hyo-Jin
HJ
D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D001752:Blast Crisis / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor / Q000166:cytology* / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D014178:Translocation, Genetic
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate