ABSTRACT
Objective To analyze the genetic characteristics of chromosomes and related fusion genes in acute myeloid leukemia (AML) (non-M3), and to evaluate the prognosis of patients with chemotherapy of DA regimen with different doses of daunorubicin. Methods Fifty-six patients with newly diagnosed non-M3 AML from January 2013 to January 2015 were collected. Adopted short-term culture method was used to treat bone marrow, R-binding chromosome karyotyping was used to detect cytogenetic. Thirty-one types of fusion gene were identified by PCR and 10 % agarose gel electrophoresis. All patients treated by DA regimen were divided into group A, group B and group C according to different dosage of daunorubicin. Then, complete remission (CR) rate and survival time in the 3 groups were observed. The effect of cytogenetic and molecular biology abnormality on the chemotherapy, CR rate and overall survival (OS) of the 3 groups were analyzed by the chi-square test. Results Among the 56 patients, 18 cases (32.1%) had abnormal chromosome karyotype, 6 cases (10.7 %) had abnormal number of chromosome, 16 cases (28.6 %) had abnormal structure of chromosome, and 4 cases (7.1 %) had both abnormal number and structure of chromosome. Meanwhile, the most common abnormal structure was t(8;21), and the most common abnormal quantity were+8, -Y. Detective rate of genetic abnormality was raised to 62.00 % through fusion gene and chromosome karyotype analysis. The total CR rate of DA-induced chemotherapeutic regimen was 73.2 %, and the two-year OS rate was 42.9%. The remission rate of chemotherapy in the middle-risk group was significantly lower than that in the low-risk group (χ 2 = 8.976, P = 0.002), but there was no significant difference between the low-dose chemotherapy group and the standard dose chemotherapy group (P>0.05). The standard dose group showed a significant advantage in the OS rate (χ2= 8.045, P= 0.005). Conclusions Adult acute leukemia has its unique cytogenetic characteristics, which can assist in guiding clinical diagnosis, classification and prognosis. The prognosis of middle-risk patients is significantly lower than the low-risk group. Low-risk patients could benefit from a reduced dose of DA regimen, but the standard dose DA regimen has a significant advantage in long-term survival.
ABSTRACT
Objective To investigate the effect of CCAAT/enhancer-binding protein homologeus protein (CHOP) in Tan Ⅱ A treated acute promyelocytic leukemia (APL) cells.Methods APL cell differentiation was monitored by morphology and membrane differentiation antigens; expression of CHOP was inhibited by siCHOP; mRNA and protein expression of CHOP in Tan Ⅱ A-intervened APL cells were examined by RT-PCR and Western blot.Results Expression of CHOP was increased in Tan Ⅱ A induced differentiated APL cells (proteins levels 1.933±0.987 vs 0.537±0.110,F =114.852,P < 0.01,mNRA levels 1.587±0.815 vs 0.713±0.090,F =52.256,P < 0.01),combination of CHOP gene silencing with Tan Ⅱ A treatment induced strong APL cell differentiation [(50.767±1.241) % vs (16.167±2.122) %,F =989.431,P < 0.05] and apoptosis [(89.233±5.581) % vs (27.433±2.957) %,F =308.961,P < 0.05].Conclusion CHOP acts as a negative regulator in Tan Ⅱ A induced differentiation.Inhibition of CHOP may be a promising therapeutic strategy.