Glucocorticoid-induced granzyme A expression can be used as a marker of glucocorticoid sensitivity for acute lymphoblastic leukemia therapy.
The ability of glucocorticoids (GC) to efficiently kill lymphoid cells has led to their inclusion in essentially all chemotherapy procedures used to treat acute lymphoblastic leukemia (ALL). GC sensitivity is an important prognostic factor in ALL treatment, and it is used to classify patients into risk groups. Clinical assessment for GC sensitivity is very time-consuming, however. We have recently found that granzyme A (GZMA) mediates GC-induced apoptosis in ALL-derived cell line 697. In this study we examined the correlation between GC sensitivity and GC-induced GZMA expression by using seven established cell lines derived from ALL patients. The apoptosis assay showed four cell lines were GC-sensitive and three were GC-resistant. GC treatment markedly enhanced GZMA expression in GC-sensitive cell lines only, and not in GC-resistant cell lines. GC-induced GZMA expression also correlated well with the amount of GC-induced apoptosis. GC-induced GZMA expression could thus be a useful early biomarker for "personalized" ALL therapy.
Myoumoto
Akira
A
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
Nakatani
Kaoru
K
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
Koshimizu
Taka-Aki
TA
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
Matsubara
Hiroshi
H
Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Adachi
Souichi
S
Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Tsujimoto
Gozoh
G
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan. gtsuji@pharm.kyoto-u.ac.jp.
D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D053804:Granzymes / Q000235:genetics*; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
D005938:Glucocorticoids; D012333:RNA, Messenger; D053804:Granzymes