Study Of Correlation Between Expression Of C-kit Receptor And Acute Leukemia

Objective: (1) To investigate the expression of c-kit receptor in newly diagnosed acute leukemia patients and the effects of remission induction therapy on its expression. (2) By detecting AML1/ETO fusion gene in newly diagnosed acute leukemia patients in Jiangsu Institute of Hematology, We investigated its expression and its relativity with the expression of c-kit receptor in order to further explore their roles in leukemogenesis.Methods: (1) Bone marrow mononuclear cells from 104 newly diagnosed acute leukemia patients before and after therapy as well as 11 nonmalignant patients with normal bone marrow morphology were detected for the expression of c-kit receptor by reverse transcriptase polymerase chain reaction (RT-PCR). Then we traced its expression in some patients when they achieved complete remission. SPSS 13.0 software package was used to perform Chi-square test or Fisher's exact probability analysis in order to compare the differences of expression rate between acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) patients and the changes of expression rate before and after therapy. Meanwhile we compare the differences of first complete remission rate between c-kit receptor positive and negative groups. (2) AML1/ETO fusion gene in AML patients was detected qualitatively by multiple PCR. Cross-tabulation and chi-square test,kappa test were designed randomly to appraise the expression of the fusion gene and its relativity with c-kit receptor, Fisher's exact probability analysis was used to compare the first complete remission rate with different expression status of AML1/ETO fusion gene and c-kit receptor.Results: (1) 50 of the 78 newly diagnosed AML patients expressed c-kit receptor, the total expression rate was 64.1%. Of them, M1 10/14 (71.4%), M2 26/38 (68.4%), M3 8/12 (66.7%), M4 3/7 (42.9%), M5 3/7 (42.9%). After treatment, 41of the 50 c-Kit receptor positive patients changed to be negative (82.0%); Of the 52 patients who achieved complete remission, 5 still remained to be c-kit receptor positive, the positive rate was 9.6%. The difference of positive rate between prior treatment and achieving complete remission was significant.(P<0.0001). We surveyed 2 patients dynamically whose c-kit receptor were continued to be positive after CR, they relapsed after 5,8 months respectively, 2 patients whose c-kit receptor changed to be negative after CR switched to be positive after relapse. (2) 3 of the 26 newly diagnosed ALL patients expressed c-kit receptor, the total expression rate was 11.5%. (3) All of the 11 patients in the controlled group were c-kit receptor negative.(4) Of the newly diagnosed patients, the positive expression rate of c-kit receptor was higher than ALL patients as well as controlled group with normal bone marrow morphology, the difference was significant.(P<0.0001).(5)Of the AML patients, the CRR after one course of treatment in c-kit receptor positive patients was 58.0%, and the CRR after one course of treatment in c-kit receptor negative patients was 82.1%, the difference was significant between the two groups(.P=0.0300). (6) Of the 91 patients with statistic informations, 49 had different abnormal chromosomes. The incidence of abnormal chromosomes in c-kit receptor positive patients was 64% (32/50) , while the incidence of abnormal chromosomes in c-Kit receptor negative patients was 41.5% (17/41), the difference was significant between the two groups.(P=0.0319). (7) Of the 38 M2 patients, 26 were c-kit receptor positive (68.4%), and 20 were AML1/ETO fusion gene positive (52.6%), 18 coexpress the two (47.3%) . 10 neither express AML1/ETO fusion gene nor c-Kit receptor (26.3%), they were positive correlation in M2 leukemia(kappa=0.4633, P=0.0026).Conclusions: (1) The positive rate of c-kit receptor in AL was higher than nonmalignant hematologic diseases dramatically, and the positive rate in AML was higher than ALL, which could be served as a reference mark to discriminate the two. (2) The first complete remission rate in c-kit receptor positive patients was lower than c-kit receptor negative patients which could be be served as a reference mark to judge the prognosis. (3) Combining other index, the dynamic changes of c-kit receptor was of certain help in detecting MRD in leukemia. (4) The relativity of c-kit receptor and AML1/ETO fusion gene indicated that they played an important role in leukemogenesis. The combined role of the two might be one of the pathogenesies in leukemia.