In vitro resistance of leukaemic blasts to prednisolone in bcr-abl positive childhood acute lymphoblastic leukaemia.
OBJECTIVE
Although the outcome of children with acute lymphoblastic leukaemia (ALL) has improved dramatically over the last decade, some children still fare poorly and relapses are seen. The sensitivity of leukaemic cells to corticosteroids has emerged as an important prognostic factor in ALL. The t(9,22) translocation, resulting in the bcr-abl fusion gene, is a non-random translocation found in B-lineage acute lymphoblastic leukaemia. It is also known to be an independent poor prognostic factor for long-term disease free survival. We studied the association between the presence of bcr-abl fusion gene and in vitro prednisolone resistance in children with B-lineage acute lymphoblastic leukaemia at diagnosis.


METHODS
A total of 23 children (aged 1-16 yr, median age: 12 yr) with B-lineage acute lymphoblastic leukaemia at diagnosis were included in the study. The presence of bcr-abl fusion gene was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and the in-vitro resistance to prednisolone was measured by short term colorimetric methyl thiazol tetrazolium (MTT) assay.


RESULTS
A median LD50 (lethal dose for 50% cells) for prednisolone in bcr-abl positive children (n=7) was 1.6 mg/ml (range: 0.25-5.0 mg/ml) and that of bcr-abl negative children (n=16) was 0.35 mg/ml (range 0.62-1.0 mg/ml). The median LD50 for prednisolone differed significantly between the bcr-abl positive and negative groups of children with acute lymphoblastic leukaemia (P<0.005).


CONCLUSIONS
This is probably the first report to show that leukaemic blasts of bcr-abl positive children with ALL are about four-fold resistant to prednisolone as compared to blasts from bcr-abl negative children. This suggests that one of the reasons for the poor prognosis of bcr-abl positive ALL could be a lower steroid sensitivity.
Gupta
Mamta
M
Department of Immunology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Kumar
Anil
A
Dabadghao
Sunil
S
D000293:Adolescent; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003601:Cytotoxicity Tests, Immunologic; D019008:Drug Resistance, Neoplasm; D005260:Female; D016313:Genes, abl; D006801:Humans; D007223:Infant; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008297:Male; D010677:Philadelphia Chromosome; D011239:Prednisolone / Q000494:pharmacology / Q000627:therapeutic use*; D011379:Prognosis
D018931:Antineoplastic Agents, Hormonal; D011239:Prednisolone