Role of Lyn kinase in imatinib-resistant chronic myelogenous leukemia / 中国实验血液学杂志

This study was aimed to explore the role of Lyn kinase in imatinib-resistant CML. Lyn, BCR/ABL fusion gene and chromosomes were detected in 76 CML patients being divided into imatinib-resistant, newly diagnosed and effective groups, and then the expression of Lyn was compared and the relationship between Lyn and clinical characteristics, BCR/ABL fusion gene and chromosomes were analyzed. The results indicated that all the 76 CML patients and 10 normal persons expressed Lyn. Lyn expression in imatinib-resistant patients was significantly higher than that in normal persons, newly diagnosed patients and imatinib-effective patients (P < 0.05). However, there was no statistically significant difference between newly diagnosed patients, effective patients and normal persons (P > 0.05). Lyn expression had no significant correlation with median age, sex, median hemoglobin level, and median platelet level, percentage of peripheral blasts, spleen size (P > 0.05). The Lyn expression was related with the higher count of peripheral blood leukocytes at new diagnosis (P < 0.05). There was no obvious relationship between Lyn and BCR/ABL levels (P > 0.05). There was 1 case with chromosome abnormality in t(6;22) and t(2;9) in 10 imatinib-resistant CML patients, coexisting with Ph chromosome. Ph chromosome only existed in the remanent 9 cases of CML. It is concluded that both the CML patients and normal persons express Lyn. Lyn is over-expressed in imatinib-resistant CML. The increased Lyn expression is closely related with higher WBC count.

Expression of DNA-dependent protein kinase catalytic subunit in adult acute leukemia and its significance / 中国实验血液学杂志

This study was aimed to explore the expression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) in adult acute leukemia and its correlation with clinical characteristics, karyotype and prognosis. Indirect immunofluorescent cytometry was used to detect the expression of DNA-PKcs in bone marrow mononuclear cells of 105 patients with acute leukemia before chemotherapy and 41 of them after 2 cycles of chemotherapy. Cytogenetic data were obtained from 26 of them by R band karyotypic analysis. The results showed that the expression of DNA-PKcs was correlated with higher WBC count level in peripheral blood (p < 0.05), but was not obviously associated with median age, gender, percentage of bone marrow blasts, clinical classification, median hemoglobin level and median platelet count (p > 0.05). The middle and strong positive expression of DNA-Pkcs in non-remission group was significantly higher than that in remission group (p < 0.05). The positive rate of DNA-PKcs in abnormal chromosome group was significantly higher than that in chromosome normal group (p < 0.05). It is concluded that the DNA-PKcs expression level is closely related with the increased WBC count, and the expression of DNA-PKcs is correlated also with karyotype and clinical prognosis in adult acute leukemia.

Expression of angiotensin-II type 1 receptor at1 mRNA in myeloid leukemia / 中国实验血液学杂志

This study was aimed to explore the expression level of angiotensin-II type 1 receptor (AT1) mRNA in bone marrow of myeloid leukemic patients, and its correlation with the proportion of leukemia cells in samples and Hb, WBC, Plt counting in peripheral blood. 51 samples, including 36 AML, 7 CML, and 8 samples of non-malignant hematological diseases as control group were collected. The expression of at1 mRNA was detected by real time-PCR; the expression levels of at1 gene in AML and CML groups were relatively quantitatively analyzed by using 2(-ΔΔCT) and were compared with control group. The results showed that the expression levels of at1 mRNA in AML, CML and control groups were 0.038 ± 0.076, 0.033 ± 0.039, 0.281 ± 0.366, respectively. at1 gene expression in the myeloid leukemic group was significantly lower than that in the control group. The expression level of at1 mRNA in AML was negatively correlated with the proportion of leukemia cells and positively with Hb level in peripheral blood. It is concluded that at1 gene may play a minor role in leukaemogenesis, however, may promote erythropoiesis.

Therapeutic effect of priming induction regimen of CAG for newly diagnosed acute myeloid leukemia in elderly patients / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the clinical efficacy and toxicity of priming induction regimen of CAG for newly diagnosed acute myeloid leukemia (AML) in elderly patients.@*METHODS@#Seventy-five patients with newly diagnosed AML were divided into 2 groups: 34 were treated with priming induction regimen CAG and the other 41 were treated with 2 classic routine chemotherapy regimens including pirarubicin+cytarabine (TA) and homoharringtonine+cytarabine (HA). All patients had a 14 day interval between the 2 courses of chemotherapy.@*RESULTS@#The complete remission rate after 2 courses of induction therapy in patients with the priming induction regimen CAG and the total efficacy rate was significantly higher than that of the routine chemotherapy patients(67.6% vs. 39%; 82.4% vs. 56.1%). Patients with unfavorable karyotypes had poor chemotherapy efficacy. The 3-year disease-free-survival (DFS) time was longer in patients with AML treated with priming induction regimen CAG than in patients treated with 2 classic routine chemotherapy regimens. Except for the muscular soreness, the hematological and non-hematological side effects in the CAG priming induction group were significantly fewer than those in the routine chemotherapy group.@*CONCLUSION@#The priming induction regimen of CAG has a significantly higher complete remission rate and an efficacy rate, fewer side effects, milder chemotherapy intensity and is more sensitive to chemotherapeutic drugs than those of the routine chemotherapy. It can shorten the duration of agranulocytosis and decrease infectious complications and increase the sensitivity of leukemia blast cells to chemotherapeutic drugs.

Clinical significance of NF-kappaB continual activity and expression of WT1 and MDR1 in acute nonlymphocytic leukemia / 中国实验血液学杂志

The study was aimed to explore the NF-kappaB continual activity and the expression of WT1 and MDR1 in acute non-lymphocytic leukemia (ANLL) patients, and to investigate if the three factors affect the curative effect of ANLL together as to provide some theoretical basis for finding new measures to improve the curative effect of refractory ANLL. The bone marrow samples of 45 ANLL patients was collected. 45 patients including 20 primary ANLL patients (A group) and 25 refractory ANLL patients. Refractory ANLL patients were divided into 2 sub-groups (B, C groups). The primary patients who was no effect after more than two courses of treatment were taken as group B, and the patients with more than two relapses were taken as group C. At the same time, 15 patients with simple iron deficiency anemia were collected as negative control. The NF-kappaB continual activity was measured by using electrophoretic mobility shift assay (EMSA) and the expressions of WT1, MDR1 were detected by reverse transcriptase polymerase chain reaction (RT-PCR). The results showed that the activity of NF-kappaB and the expressions of WT1, MDR1 were not detected in 15 samples of simply iron deficiency anemia subjects. The NF-kappaB continual activity, the expression levels of WT1 and MDR1 in the refractory group were significantly higher than that in primary group (P<0.001). But the NF-kappaB continual activity, the expression of WT1 gene and MDR1 gene were not significantly different between group B and group C (P>0.05). By assaying the relativity between the them the NF-kappaB continual activity and the expression of WT1 or MDR1 had positive correlation in ANLL patients. It is concluded that the NF-kappaB continual activity, the overexpression of WT1 and MDR1 may be one of the reasons causing poor curative effect in acute non-lymphocytic leukemia. The NF-kappaB continual activity and the expression of WT1, MDR1, all show positive correlation in ANLL patients.

Effect of recombinant human interleukin 11 on the platelet after hematopoietic stem cell transplantation in patients with leukemia / 中南大学学报(医学版)

OBJECTIVE@#To explore the effect and toxicity profile of recombinant human interleukin 11(rhIL-11) on the platelet after hematopoietic stem cell transplantation in patients with leukemia.@*METHODS@#Twenty-four patients with acute or chronic leukemia treated by allogeneic peripheral blood stem cell transplantation (PBSCT) were randomly divided into a test group and a control group. The patients in the test group were treated with rhIL-11 since the 13th day after PBSCT (1.5mg/d),while the control group were given symptomatic treatment.@*RESULTS@#The average time for the platelet to recover to the level of 20 x 10(9)/L was 20.8 days in the test group, and 26.0 days in control group respectively, there was significant difference (P<0.01). The average time for the platelet to recover to the level of 50 x 10(9)/L was 25.7 days in the test group, and 32.3 days in the control group respectively, there was also significant difference (P<0.01). The average time for the platelet transfusion was 2.2 in the test group, 4.1 in the control group, and there was significantly different (P<0.01). The average number of megakaryocytes was 12.2 in the test group, 4.8 in the control group on 30th day after the transplantation,and there was significant difference(P<0.01). The main side effects of rhIL-11 were nausea, vomit, debility, headache, dizzy and pain of injection site, and the degree was all Iapproximately II grade.@*CONCLUSION@#rhIL-11 has definite recuperative effect on the recovery of the platelet after PBSCT. There is little side effect, and it can be accepted.

Renin angiotensin system in bone marrow of patients with aplastic anemia / 中国实验血液学杂志

Renin-angiotensin system (RAS) has been shown to be involved in the growth, production, proliferation and differentiation of the bone marrow (BM) hematopoietic cells, while aplastic anemia (AA) is a disease in which proliferation ability of the BM hematopoietic cells is damaged with defective hematopoietic microenvironment. To investigated the pathogenesis of AA, the rennin activity, angiotensin I (Ang I) and angiotensin II (Ang II) concentration in peripheral blood and BM of 22 AA patients were detected by radioimmunoassay, 16 nonhematological disease patients with normal blood counts and BM picture were used as control, and the difference between two groups was compared. The results showed that BM Ang II concentration in the AA patients was significantly lower than that in the control (P < 0.01). In nonhematological disease patients, Ang II concentration in BM was significantly higher than that in peripheral blood, the renin activities and Ang I concentrations were not significantly different in the two groups (P > 0.05). In conclusion, the decreased BM Ang II concentration in AA patients may be involved to the pathogenesis of AA.

Inhibitory effect of daunorubicin enhanced by PDTC on drug-resistant leukemic cells in vitro / 中国实验血液学杂志

To investigate the chemosensitizing effect of pyrroledithiocarbomate (PDTC) on daunorubicin in drug-resistant leukemic cells in vitro, MTT method was used to observe the changes of the proliferation of intractable leukemia MNC treated with daunorubicin (30 microg/ml) combined with PDTC (25, 50 or 100 micromol/L). The results showed that inhibiting rate of daunorubicin combined with PDTC(25, 50 or 100 micromol/L) on drug-resistant leukemic cells was significantly higher than that of daunorubicin alone (P < 0.05). Among the three different doses of PDTC, the concentration of 50 micromol/L of PDTC inhibited the proliferation of drug-resistant leukemic cells significantly. In conclusion, PDTC can sensitize anti-tumor effect of daunorubicin in vitro. The concentration of 50 micromol/L of PDTC has stronger chemosensitizing effect on daunorubicin than that of the other concentrations of PDTC (25 micromol/L or 100 micromol/L) in vitro.