Expression of MiR-155 in Tissue of Patients with Diffuse Large B-Cell Lymphoma and Its Effect on Cell Biological Characteristics / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of miR-155 in patients with diffuse large B-cell lymphoma (DLBCL), and to explore the effect of transfection of miR-155 inhibitor on the biological characteristics of DLBCL cells.@*METHODS@#A total of 76 patients with DLBCL treated in our hospital were selected from April 2013 to December 2017. In the same time, 40 cases of lymph node reactive hyperplasia (LNRH) were selected as control group. DB cells were cultured and divided into miR-155 inhibitor, negative control and blank groups. The expressions of miR-155 in DLBCL, negative and blank control groups were detected by using real-time PCR, the cell proliferation was detected by MTT assay, the apoptosis was detected by flow cytometry, and the cell migration and invasion were detected by Transwell assay.@*RESULTS@#The relative expression level of miR-155 in tissues of DLBCL patients was significantly higher than that in tissne of controls (1.93±0.16 vs 1.01±0.09) (t=33.991, P=0.000). The expression level of miR-155 increased (P＜0.05) in DLBCL patients with LDH level abnormarity, BCL-2, MUM1, Ki-67≥50%, non-GC type, Ann Arbor stage III-IV, extranodal lesion number≥2 and IPI score 3-5. The relative expression level of miR-155 in the miR-155 inhibitor group was lower than that in the negative control group and the blank group (P＜0.05). The absorbance (A) values at 24, 48, 72 and 96 h of culture in the miR-155 inhibitor group were lower than those in the negative control group and the blank group (P＜0.05), while the apoptotic rate was higher than that in the negative control group and the blank group (P＜0.05). Both the migrating cells and invading cell number in the miR-155 inhibitor group were lower than those in the negative control group and the blank group (P＜0.05).@*CONCLUSION@#The miR-155 highly expresses in DLBCL tissue, which relates with tumor malignancy and invasion progression. The specific inhibition of miR-155 expression in DB cells can reduce cell proliferation, accelerate cell apoptosis, and inhibit cell migration and invasion.

Clinical Efficacy and Prognostic Factors of Decitabine for Treatment of Myelodysplastic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical efficacy of decitabine for treatment of patients with myelodysplastic syndrome (MDS) and factors predicting the prognosis.@*METHODS@#The clinical data of 87 patients with MDS treated with decitabine were analyzed retrospectively. The hENT1 mRNA expression and TP53 gene mutation were detected by Q-PCR and gene target sequencing, respectively. The relationship of clinical characteristics and molecular indicators with the clinical response to decitabine was analyzed.@*RESULTS@#In treatment for median 4 (2-17) courses, a total 51 patients (58.6%) showed therapeutic responses, including CR in 17 cases, PR in 12 cases, mCR in 9 cases, HI in 13 cases; 36 (41.4%) patients showed non-response. Univariate analysis showed that the patients with the complex karyotype, monosomal karyotype, chomosome 7 abnormality and Plt count doubling after 1 course treatment had a high CR rate, while the patients with relative high risk by IPSS (intermediate risk 2+ high risk), complex karyotype and Plt count doubling after 1 course had much more high overall remission rate (ORR). The expression level of hENT1 mRNA in MDS patients with response was significantly higher than that in patients without response ［(1.78±1.45 (2) vs 0.96±0.97 (2)(P= 0.002)］. Among 51 patients with therapeutic response, the expression level of hENT1 mRNA in CR group was higher than that in non-CR group ［(2.58±1.44 (2) vs 1.39 ±1.3 (2), P= 0.005)］. Among 52 patients in relative high risk (intermediate risk 2 +high risk), the median OS time of patients with high hENT1 mRNA expression was significantly longer than that of patients with low hENT1 mRNA expression (31 vs 12 months)(P<0.001). Among 87 patients received decitabine treatment, the TP53 gene mutation occured in 11 (12.6%) patients. The ORR in patients with TP53 mutation was high (P=0.04), moreover the patients with TP53 mutation more easily gained CR (P<0.001). Multivariate logistic regression model showed that the complex karyotype, Plt count doubling after 1 course treatment, TP53 mulation and high expression of hENT1 mRNA were the independent prognostic factors for predicting the CR after decitabine treatment.@*CONCLUSION@#IPSS staging, complex karyotype, Plt count doubling after 1 course treatment and hENT1 mRNA expression, TP53 gene mutation can be used to predict the tharapeutic efficacy of dectitabine for treatment of MDS.

Expression of HOXB4, PRDM16 and HOXA9 in Patients with Acute Myeloid Leukemia and Its Clinical Significance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate HOXB4, PRDM16 and HOXA9 gene expression in patients with acute myeloid leukemia (AML) and its clinical significance.</p><p><b>METHODS</b>Real-time quantitative PCR (RT-qPCR) with SYBR Green assay was used to detect the expression of HOXB4, PRDM16 and HOXA9 gene in AML patients (40 cases), the patients with complete remission (9 cases) and patients with non-malignant hematologic diseases as control (10 cases). The relationship between the expression levels of gene HOXB4, PRDM16, HOXA9 and clinical features was investigated by statistical analysis.</p><p><b>RESULTS</b>The gene expression levels of HOXB4, PRDM16, HOXA9 in newly diagnosed or relapsed AML patients were significantly higher than those in patients with non-malignant hematologic disease (P < 0.05). It was observed that the expression of HOXB4 gene in newly diagnosed or relapsed patients positively correlates with leukemic blasts in bone marrow (r = 0.39). The expression levels of HOXB4, PRDM16 and HOXA9 positively correlate with each other. There was statistical significance among gene expressions in different phases (newly diagnosed, relapse, remission). No correlation was observed between expression levels of HOXB4, PRDM16, HOXA9 and chromosome risk status. It was noticed that expression levels of HOXB4, PRDM16, HOXA9 genes were lower in the patients achieved remission after two courses of chemotherapy than those in the other. And high expression group of each gene had a lower remission rate than that in the low expression group.</p><p><b>CONCLUSION</b>The expression level of HOXB4, PRDM16, HOXA9 genes and leukemic blasts somewhat correlate with curative effect and prognosis. The expression of HOXB4, PRDM16, HOXA9 genes is higher in newly diagnosed and relapsed leukemia patients, and lower in the patients acquired CR/PR. High expression of HOXB4, PRDM16, HOXA9 genes predicts an adverse prognosis.</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>

Recombinant human thrombopoietin in combination with cyclosporin A as a novel therapy in corticosteroid-resistant primary immune thrombocytopenia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The management of patients with refractory immune thrombocytopenia (ITP) is challenging, as there is no standard treatment option. The aim of this study was to investigate the efficacy of recombinant human thrombopoietin (rhTPO) in combination with cyclosporin A (CsA) for the management of patients with corticosteroid-resistant primary ITP.</p><p><b>METHODS</b>Thirty-six patients with corticosteroid-resistant ITP were randomly divided into an observation group and control group. In the observation group, 19 patients received subcutaneous injection of rhTPO at a dose of 1 µg/kg (300 U/kg) once daily up to day 14. Simultaneously they also received oral CsA at a dose of 1.5-2.0 mg/kg twice daily for three months. In the control group, rhTPO alone was administered subcutaneously at 1 µg/kg once daily in the other 17 ITP patients for 14 consecutive days and then the treatment was withdrawn.</p><p><b>RESULTS</b>There was no significant difference in the response rate at the end of the first week after treatment initiation between the observation group and the control group (63.2% vs. 58.8%, P > 0.05), neither was there at the end of the second week (89.5% vs. 94.1%, P > 0.05). However, the relapse rate in the observation group was significantly lower than that in control group at the end of the first (17.7% vs. 50.0%, P < 0.05), second (29.4% vs. 68.8%, P < 0.05) and the third month (29.4% vs. 87.5%, P < 0.01). In addition, rhTPO plus CsA were well tolerated and adverse events recorded were mild.</p><p><b>CONCLUSIONS</b>Combination therapy with rhTPO and CsA was effective in the management of patients with corticosteroidresistant ITP, with a relatively short time to response and low recurrence rate. It might be considered as a potential secondline treatment regimen for ITP.</p>

Prognostic power of abnormal cytogenetics for multiple myeloma: a multicenter study in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma (MM). Interphase fluorescence in situ hybridization (i-FISH) has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique (CC). To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China.</p><p><b>METHODS</b>All 672 patients were systematically screened for the following genomic aberrations: del(13q), IgH rearrangement, del(p53) and 1q21 amplifications.</p><p><b>RESULTS</b>The analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations (48.4%), -13/13q- (37.6%), hyperdiploidy (36.6%), hypodiploidy (30.1%) and IgH rearrangements (23.7%). The most frequent abnormalities by FISH was del(13q), which was found in 60.4% patients, whereas IgH rearrangement, 1q21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet (P = 0.015), hyperdiploidy was associated with low level of serum albumin (P = 0.028), and IgH rearrangement by FISH was associated with high level of β2 microglobulin (P = 0.019). Moreover, 1q21 amplification and del(p53) by FISH conferred a high incidence of progressive disease (PD) after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival (PFS) (P = 0.036). No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS.</p><p><b>CONCLUSIONS</b>Chinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.</p>

Serum level of angiogenesis-related cytokins in patients with myelodysplastic syndrome / 中国实验血液学杂志

To study the serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients with myelodysplastic syndrome (MDS), serum from 43 MDS patients was examined by enzyme linked immunosorbent assay (ELISA). The results showed that serum levels of VEGF, bFGF in MDS patients were significantly elevated compared with normal control. Serum levels of VEGF and bFGF in RAEB patients and RAEBT patients were higher than that in RA patients and RAS patients (P < 0.05). No significant difference of serum levels of VEGF and bFGF was found between RAEBT patients and acute myeloid leukemia (AML) patients. The serum levels of VEGF and bFGF were correlated with the affected peripheral blood cells and the proportion of blast cells in bone marrow. There was positive correlation between serum VEGF and bFGF levels. It is concluded that the secretion of VEGF and bFGF in MDS patients is elevated and the serum levels of VEGF and bFGF are related to the classification and prognosis in MDS.

Expression of lung resistance protein and multidrug resistance protein genes in bone marrow cells of acute leukemia patients and its clinical significance / 中国实验血液学杂志

To study the expression of lung resistance protein (LRP) and multidrug resistance protein (MRP) genes in bone marrow cells in patients with acute leukemia and its clinical significance, expression of LRP and MRP mRNA in bone marrow cells from 47 cases of acute leukemia, including 10 refractory or relapsed cases, and 7 normal individuals were determined by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). The result s showed that expression of LRP gene was negative in normal individuals. LRP mRNA level in newly treated cases of acute myelocytic leukemia and refractory or relapsed cases was significantly higher than that in normal individuals, increased LRP mRNA level has correlation with lower sensitivity to initial chemotherapy and was associated with reduced overall survival rate. Complete remission (CR) rate in LRP positive patients was lower than that in negative cases. The level of LRP expression was correlated with that of MRP mRNA. In conclusion, the expression of LRP mRNA can predict the treatment outcome and prognosis for acute myelocytic leukemia, prognosis was even worse in LRP and MRP linked expression cases, therefore, LRP was an important resistant factor, determination of LRP and MRP expression can help us to evaluate the prognosis and choose chemotherapy program.