Significance Of The Bcr Gene And Bcr/abl Gene In The Occurrence And Progress Of The CML

Background: Chronic myeloid leukemia (CML) is a clonal malignant myeloproliferative disorder of the hematopoietic stem cells, characterized by the presence of the abnormal Ph chromosome. As the hallmark of cellular genetics for CML, the Ph chromosome is a translocation between chromosomes 9 and 22, t(9;22)(q34.1;qll.21), in which the c-abl proto-oncogene on chromosome 9 was reciprocally translocated to the breakpoint cluster region (bcr ) of the bcr gene on chromosome 22 resulted in the formation of fusion bcr-abl gene. The bcr/abl gene encoded P2l0bcr/abl protein with higher tyrosine protein kinase activity than normal P145 protein and P2iobcr/abl protein has the function of anti-apoptosis and anti-adhesiveness. It is the main pathogenesis in the occurrence and progression of CML. The further investigation showed that bcr gene was a negative regulator of the Bcr-Abl fusion gene, and its expression can inhibit the activity of P2l0bcr/abl protein. It has been reported that the bcr-abl fusion gene has been detected by nested reverse transcription polymerase chain reaction (nested RT-PCR) in normal healthy individuals, but it is not known why the normal healthy individuals with bcr/abl mRNA positive don't suffer with CML.Objectives: To explore the reason why normal individuals with bcr/abl fusion gene don't suffer with leukemia and the effect of bcr and bcr/abl gene to the pathogenesis of CML, we studied the bcr/abl mRNA expression in the normal healthy individuals, including the members from the families with CML, and the levels of bcr/abl and bcr mRNA in the patients with CML inthe chronic, accelerated or blast phase.Methods: 1. The expression of bcr/abl mRNA had been detected by nested RT-PCR in the normal healthy individuals, including the members from the families with leukemia. 2. The levels of bcr/abl and bcr mRNA had been estimated by semi-quantitative RT-PCR in the patients with CML in the chronic, accelerated and blast phase. 3. The data from our study were analyzed by SPSS 10.0.Results: 1. The rate of individuals with positive bcr/abl mRNA was 40.00% and 45.45% in families with and without leukemias, respectively. It showed no significant difference by the analysis of Chi-Square Test. Some individuals were bcr/abl mRAN positive and others negative in the same family with leukemia. 2. The levels of bcr/abl and bcr mRNA in the chronic phrase were lower than that in the accelated and blast phase (P<0.01). 3. Our study showed the expression levels of bcr mRNA is relatively insufficient in comparison with the levels of bcr/abl mRNA in the accelated and blast phrase.Discussion: There is no significant difference of the positive rate of bcr/abl mRNA between the normal healthy individuals from the families with and without leukemia. In the same family, some individuals were bcr/abl mRNA positive and the others were negative. According to these facts, bcr/abl gene was considered to be acquired rather than to be inherited in the normal individuals with bcr/abl mRNA positive. The reason that the normal healthy individuals with bcr/abl mRNA don't develop leukemia was assumed that bcr/abl gene could induce the expression or higher expression levels of the bcr gene and bcr gene was a negative regulator of bcr/abl gene according to our results and the literatures. The expression or higher expression of bcrgene can induce the apoptosis of the haematopoietic stem cells with bcr/abl gene, which protects the individuals with bcr/abl gene from leukemia. The expression levels of bcr/abl and bcr mRNA gradually increased, but the expression levels of bcr mRNA was relatively insufficient in comparison with the expression of bcr/abl mRNA during the progression of CML, which is considered the main pathogenesis about the aggravation and progression of CML.