Study Of ABL Kinase Gene Polymorphism In Ph Chromosome-positive Leukemias

Objective: To study expressions of BCR-ABL fusion gene in Ph+leukemia patients and significance of ABL kinase domain point mutation inimatinib resistance patients. Methods:1RQ-PCR was used to detect expressionsof BCR-ABL mRNA in Ph+leukemia patients.2Nested reversetranscriptase-polymerase chain reaction(RT-PCR)was performed on bone marrowor blood samples from patients of different phases to amplify the ABL kinasedomian,followed by direct sequencing and sequence homologous analysis。Resultsof RT-PCR and mutation detection combined with clinical features were undercorrelation analysis. Results:36cases of CML patients are detected by RT-PCR,there are32cases with expressions of BCR-ABL fusion gene, positive rate is91.4%. The relative quantity expression of BCR-ABL fusion gene in CML patientsof different phases is analysed by ONE-WAY ANOVA, and amplification volumeof BCR-ABL fusion gene is richer in blast crisis phase than those in chronic phaseand accelerated phase(p<0.005, p<0.05); in5cases of ALL patients, there are4cases with positive expression, and among which there are2cases of patients withco-expression of P190and P210.2.ABL kinase domain of BCR-ABL gene positivesamples is amplified by nest PCR,mutations are detected through direct sequencingmethod and sequencing resultes reveal no mutations.Conclusion:1. Expressionquantity of BCR-ABL fusion gene mRNA has something to do with clinical prognosis, expression level is rich in chronic phase and blast crisis patients, butwhether expression quantity is related to resistance mutation or not requires futherstudy.2. The sequencing results reveal no mutations, Which indirectly infer itsmutation may be related to imatinib.3. New detect method is used to increasedetection rate of ABL kinase domain point mutation, and several point mutationswhich are indicative of clinical resistance are optimised, and there is a long way togo to put them into use in the clinic.