In vitro efficacy of l-asparaginase in childhood acute myeloid leukaemia.
To explore the potential efficacy of l-asparaginase treatment in acute myeloid leukaemia (AML) patients, we studied the in vitro resistance of French-American-British (FAB) subtypes of childhood AML to l-asparaginase using a methyl-thiazol-tetrazolium assay. We tested leukaemic cells obtained from 177 common acute lymphoblastic leukaemia (cALL) and 228 AML children at diagnosis. The median 70% lethal dose of l-asparaginase (LD70asp) (U/ml) was 0.46 in the cALL and 6.70 in the AML samples. The median LD70asp among each FAB subtype of AML was 0.76 (M0), 0.46 (M1), 10.00 (M2), 10.00 (M3), 1.18 (M4), 1.35 (M5) and 10.00 (M7). Type M3 samples had the highest LD70asp. The LD70asp of the M2 samples was significantly higher than that of the M1, M4 and M5 samples. When the LD70asp values were classified as low (0.016-0.159), intermediate (0.16-1.59) or high (1.6-10.00), the frequency of low, intermediate or high LD70asp among the M1 samples were similar to those among the cALL samples. In conclusion, cells from AML types M1, M4 and M5 were relatively sensitive to l-asparaginase, and M1 cells were as sensitive as those of cALL, suggesting that l-asparaginase treatment may be effective for these subtypes of AML.
Okada
Shuichi
S
Department of Paediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan. sokada@hama-med.ac.jp
Hongo
Teruaki
T
Yamada
Sayuri
S
Watanabe
Chieko
C
Fujii
Yuji
Y
Ohzeki
Takehiko
T
Horikoshi
Yasuo
Y
Ito
Tsuyoshi
T
Yazaki
Makoto
M
Komada
Yoshihiro
Y
Tawa
Akio
A
D000208:Acute Disease; D000293:Adolescent; D000367:Age Factors; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001215:Asparaginase / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007223:Infant; D007928:Lethal Dose 50; D007948:Leukemia, Monocytic, Acute / Q000188:drug therapy; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D015479:Leukemia, Myelomonocytic, Acute / Q000188:drug therapy; D018655:Lymphocyte Count; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D012737:Sex Factors
D000970:Antineoplastic Agents; D001215:Asparaginase