Relationship of GSTT1 and GSTM1 Gene Polymorphisms and PAH-DNA Adducts with Pathogenesis of Multiple Myeloma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the relationship of GSTT1, GSTM1 gene polymorphisms and PAH-DNA adduct with pathogenesis of multiple myeloma.</p><p><b>METHODS</b>The bone marrow samples from 37 newly-diagnosed MM patients and 52 healthy peoples as controls were collected; the PCR-based restriction fragment length polymorphism (PCR-RFLP) method was used to detecte the polymorphism of GSTT1 and GSTM1, and to analysis their relationship with clinical characters of MM patients; the engyme linked immunosorbent assay (ELISA) was performed to detect the concentration of PAH-DNA adducts.</p><p><b>RESULTS</b>GSTT1 null and GSTM1 null genotypes increased the risk of multiple myeloma with OR 2.57 (P=0.035) and 1.37 (P>0.05) respectively. In MM patients group, GSTT1 null genotype in stage III was significantly higher than that in stages I, II (P=0.038). However, no statistically significant association was found between GSTT1 gene polymorphism and clinical characters, such as age, type, hemoglobin, β2-MG, albumin. Compared with Hb≥85 g/L of the newly-diagnosed MM patients, MM patients with Hb<85 g/L had significantly higher incidence of GSTM1 null genetype (P<0.05). The level of PAH-DNA adducts in MM patients was higher than that in controls (2358±1182 pg/ml vs 1853±996 pg/ml) (P<0.05). GSTT1 null genotype with PAH-DNA level≥2100 pg/ml showed a risk index of MM (OR=4.500, P<0.05).</p><p><b>CONCLUSION</b>GSTT1 gene may have a critical function in the development of MM, and correlates with staging of MM. GSTM1 gene polymorphism correlates with hemoglobin levels of patients with MM. The content of PAH-DNA adducts may play an important role in the pathogenesis of multiple myeloma.</p>

Clinical Efficacy of Dasatinib, Nilotinib and Imatinib in Newly Diagnosed Patients with Chronic-Phase Chronic Myeloid Leukemia: A Three-year Retrospective Analysis / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate efficacy and safety of second-generation tyrosine kinase inhibitors (TKI) dasatinib, nilotinib and imatinib in treatment of newly diagnosed patients with chronic-phase chronic myeloid leukemia (CML).</p><p><b>METHODS</b>The clinical data and follow-up results of 163 patients with chronic-phase chronic myeloid lenkemia(CP-CML) who were treated in our hospital during the nearly 3 years were analysed retrospectively, among 163 patients 47 received dasatinib, 43 received nilotinib and 73 received imatinib. The efficacy, disease progression and safety were evaluated.</p><p><b>RESULTS</b>After treatment for 3 months, the rate of complete hematologic response(CHR) in three treatment groups were 77%, 79% and 67%, respectivily, CHR at 12 months in three treatment groups were 92%, 91% and 90%, respectively. By 3 months, the rates of complete cytogenetic response(CCyR) with dasatinib and nilotinib were higher than that with imatinib (55%, 53% vs 33%)(P<0.05 for both comparisons), CCyR at 12 months in three treatment groups were 86%, 88% vs 69% (P<0.05 for both comparisons). The rates of major molecular response(MMR) for dasatinib (11%) and nilotinib (9%) by 3 months were significantly higher than that for imatinib (1%) (P<0.05 for both comparisons), MMR at 12 months in three treatment groups were 49%, 50% and 28%, respectively (P<0.05 for both comparison). Progression to the accelerated or blast phase of CML occurred in 2 (4%) patients received dasatinib, 2 (5%) received nilotinib and 6 (8%) received imatinib. The safety profiles of these 3 second-generation TKI treatments were similar.</p><p><b>CONCLUSION</b>Both dasatinib and nilotinib induced strikingly higher and faster rates of complete cytogenetic response and major molecular response, with a statistically significant difference from imatinib.</p>

Clinical significance of serum vascular endothelial growth factor and interleukin-17 in patients with multiple myeloma / 中国实验血液学杂志

The aim of this study was to investigate the clinical significance of vascular endothelial growth factor (VEGF) and interleukin-17 (IL-17) levels in patients with multiple myeloma (MM). 40 newly diagnosed MM patients were enrolled, including 9 in stage I, 18 in stage II, 13 in stage III. 25 patients were treated with VAD regimen, and 15 patients with the bortezomib and dexamethasone (BD) regimen. 20 healthy individuals as controls were enrolled in this study. The serum VEGF and IL-17 levels were determined by ELISA. The results indicated that the serum VEGF and IL-17 levels in the patients with MM were significantly higher than those in healthy controls (P < 0.01). VEGF and IL-17 levels in stage III was significantly higher than that in stage I and II (P < 0.05). There was a positive correlation between IL-17 and serum calcium β2-microglobulin or C-reactive protein (P < 0.01), and there was also a positive correlation between VEGF and serum creatinine serum Bene-Jones protein λ or urinary Bene-Jones protein λ (P < 0.01). Serum VEGF and IL-17 levels significantly decreased in MM patients after treatment, and the serum levels of VEGF and IL-17 was much lower in MM patients treated with VAD regimen than those in patients treated with BD regimen. It is concluded that the detection of serum VEGF and IL-17 levels is helpful to evaluation of the clinical stages and the severity of MM.

Expressions of cell cycle associated factors geminin and cdt1 in patients with acute leukemia / 中国实验血液学杂志

The purpose of this study was to detect the expression levels of geminin and cdt1 in peripheral blood and bone marrow from patients with newly diagnosed acute leukemia (AL), and further explore effects of them in the pathogenesis of AL. mRNA expression of geminin and cdt1 in peripheral blood and bone marrow of newly diagnosed AL patients was detected by SYBR Green real-time quantitative reverse transcription polymerase chain reaction(SYBR-RT-PCR). The results showed that mRNA expressions of both geminin and cdt1 in peripheral blood were positive in 10 out of 13 newly diagnosed ALL patients (76.92%) and in 9 out of 14 newly diagnosed AML patients (64.29%), while no positive expression of these 2 genes was detected in 10 normal controls; mRNA expression levels of geminin and cdt1 in bone marrow of newly diagnosed ALL and AML patients were 108.06 ± 67.34 and 52.37 ± 35.16, 62.66 ± 58.69 and 26.68 ± 22.29, respectively, which were higher than those in normal controls (11.81 ± 2.83 and 7.32 ± 5.77), there were significant differences (p < 0.01 and p < 0.05). mRNA expression of geminin was significantly positive related to mRNA expression of cdt1 in bone marrow of 34 newly diagnosed AL patients (r = 0.55, p < 0.01). It is concluded that mRNA expressions of geminin and cdt1 are enhanced and significantly positively related between them in bone marrow of AL patients. The over-expression of geminin and cdt1 mRNA may play an important role in pathogenesis of AL.

Expression of midkine and vascular endothelial growth factor in bone marrow of patients with multiple myeloma and its significance / 中国实验血液学杂志

The purpose of this study was to explore the expressions of midkine (MK) and vascular endothelial growth factor (VEGF) in multiple myeloma (MM), and to evaluate their relation with angiogenesis and prognosis. The expression levels of MK and VEGF in bone marrow mononuclear cells of 31 MM patients in different stages and 20 controls were detected by real-time fluorescent quantitative RT-PCR. The results showed that the MM patients had significantly higher MK and VEGF expression level than control group (p < 0.05, p < 0.01), and there was a linear relationship between MK and VEGF (r = 0.692, p < 0.01); The expression levels of MK and VEGF in stage III was significantly higher than those in stage I and stage II (p < 0.05, p < 0.01), but there was no difference between stage I and stage II (p > 0.05); MK and VEGF levels were significantly decreased in MM patients after treatment than those before treatment (p < 0.05, p < 0.01). It is concluded that the high expression of MK and VEGF is correlated with angiogenesis and prognosis of MM, and there is synergistic effect between MK and VEGF. It is supposed that the monitoring MK and VEGF expression levels may contribute to guide the treatment and estimate prognosis for MM.

Expression of CD133 in bone marrow cells of patients with leukemia and myelodysplastic syndrome / 中国实验血液学杂志

To explore the relationship between the expression of CD133 and pathogenesis of leukemia and MDS, immunocytochemistry method was used to examine the expression of CD133 in bone marrow cells of patients with leukemia and MDS. The results showed that the positive rate of CD133 in 41 acute leukemia patients was 51.2%. The expression of CD133 in AML patients (16/29, 55.2%) was significantly higher than that in control group (2/15, 13.3%). There was no significant difference in CD133 expression between CML and control group. The positive rate of CD133 in 9 patients with MDS was 55.56% (5/9). There was no significant difference between MDS and normal control. The expression of CD133 in all leukemia cells with CD34(+) was higher than that in leukemia cells with CD34(-), and there was significant difference in expression of CD133 between them (P < 0.05). The expression of CD133 had no relationship with the clinical prognostic factors such as sex, age, the percentage of leukemic cells in peripheral blood and in bone marrow, WBC counts, hemoglobin concentration, platelet counts and LDH level. It is concluded that the expression of CD133 in bone marrow cells of patients with AML is higher than that in control group. The expression of CD133 is significantly correlated with the expression of CD34. The high expression of CD133 may be an adverse prognostic factor in acute leukemia.

Expression of cyclooxygenase-2 in bone marrow cells of chronic leukemia and its significance / 中国实验血液学杂志

The study was aimed to investigate the expression of COX-2 in bone marrow cells of chronic leukemia patients and its potential pathogenetic implications. Western blot was applied for detecting COX-2 expression levels in bone marrow cells of 67 chronic leukemia patients and beta-actin expression levels. Bone marrow aspirations from 14 healthy donors were used as negative controls. The results showed that the positive rates of COX-2 in chronic-phase group of chronic myeloid leukemia (CML-CP) and in group of chronic lymphocytic leukemia (CLL) were 76.32% (29/38) and 75.86% (22/29) respectively. Both CML-CP and CLL group showed a higher expression than control group (p = 0.0000, p = 0.0000 respectively). The expression of LDH in Cox-2 positive group was higher than that in Cox-2 negative group, and the difference between the two groups was statistically significant (p < 0.001). It is concluded that the expression of COX-2 protein can be detected in bone marrow cells of CML-CP and CLL and the expression level of LDH were higher in cells of CML-CP and CLL. The expression of COX-2 may be correlated with prognosis of CML-CP and CLL.