Bcl-2 MRNA Expression And Apoptosis In Childhood Acute Iymphoblastic Leukemia

Objective Many chemotherapeutic agents are thought to exert their cytotoxic effects on tumor cells through induction of apoptosis (programmed cell death). The Bcl-2 gene is an anti-apoptotic oncogene and can prolong the survival of tumor cells by preventing apoptosis. Overexpression of Bcl-2 may therefore be implicated in resistance to chemotherapy. We studied the clinical significance of Bcl-2mRNA expression and the apoptosis index(AI) in childhood acute lymphoblastic leukemia.Methods Evaluation of Bcl-2mRNA by in situ hybridization technique and apoptot-ic index (AI) by apoptosis fluorescence assay (AFS) was carried out in a total of 30 cases and 20 normal controls.Results Bcl-2mRNA was found to be expressed in 93. 3% of the acute lymphoblastic leukemia cases, and the expression level decreased with chemotherapy, while there was no Bcl-2mRNA expression in normal controls. The Bcl-2mRNA level for the children with ALL varied widely(CV = 38. 7%). The Bcl-2mRNA level for the children with ALL were then classified as high expression group (>20%) and low expression group (^20%). Bcl-2mRNA expression was closely connected with clinical type of ALL. But there was no correlation between Bcl-2mRNA expression level and some clinical and laboratory parameters such as age, sex, initial Hb level, PLT count and blast percentage of bone marrow. Pre-treatment (spontaneous) AI of ALL was (8. 58 it 3.24)%. The AI of ALL is lower than that of normal controls (f=5. 417,P<0. 01). Bcl-2 mRNA expression level was negative consociated with AI in pre-treatment ALL (r= -0. 757, P<0. 01). AI increased after prednisone and induction chemotherapy, and the increasing degree of low Bcl-2mRNA expression cases was higher than that of high expression cases. The cases with low Bcl-2mRNA expression had higher complete remission rate of bone marrow in day 19 after induction chemotherapy(P=0. 0012). Follow-up of 5 cases who belonged to high risk type showed that they had always higher Bcl-2mRNA expression (<10%) and simultaneously had poor response to chemothera-py. And follow-up 5 cases who belonged to standard risk type were complete remission of bone marrow all along and had no invasion of other parts except bone marrow, and the Bcl-2mRNA expression level was lower (<5%).Conclusions Children with ALL have different levels of Bcl-2mRNA expression. Thus we suppose that Bcl-2 gene may be involved in the origin and development of ALL. The expression level is negative connected with AI before and after treatment, and also has close relationship with clinical type. Bcl-2mRNA expression level is closely connected with bone marrow complete remission rate in day 19 after chemotherapy. Prednisone can be used as a test of ALL children's sensitivity to chemotherapy. Follow-up of the Bcl-2 expression level may help evaluate the treatment response and estimate prognosis of children with ALL.