Role of CXCR4/STAT3 in mesenchymal stromal cell-mediated drug resistance of acute leukemia cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the role of CXCR4/STAT3 in mesenchymal stromal cell (MSC)-mediated drug resistance of AML cells.</p><p><b>METHODS</b>AML cell lines U937 and KG1a and primary AML cells were co-cultured with MSC from bone marrow of healthy donors. The AML cell lines cultured alone were used as control. Apoptosis induced by mitoxantrone was measured by flow cytometry. Expression of CXCR4 and STAT3 protein were detected by Western blot. After incubated with STAT3 inhibitor Cucurbitacin I or CXCR4 antagonist AMD3100, the apoptosis of AML cells induced by mitoxantrone was evaluated.</p><p><b>RESULTS</b>Apoptosis of AML cells (U937 and KG1a) and primary AML cells induced by mitoxantrone significantly decreased in cocultured group than that of control group [U937 cells: (20.08±1.53)% vs (45.33 ± 1.03)% , P=0.004; KG1a cells: (25.60 ± 1.82)% vs (40.33 ± 3.29)% , P=0.020]. Expression of phosphorylated STAT3 and CXCR4 protein in AML cells were upregulated in cocultured group. After addition of Cucurbitacin I into the co-culture system, the apoptosis rate of primary AML cells significantly increased. Similar results of the apoptosis rates were also detected when the inhibitor of CXCR4 AMD3100 was added to overcome the stromal cell-mediated drug resistance. Besides, the expression of p-STAT3 in AML cells after incubated with AMD3100 decreased significantly.</p><p><b>CONCLUSIONS</b>AML cells cocultured with MSC leads to the up-regulation of phosphorylated STAT3 and CXCR4 proteins, which resulted in AML cells resistance to chemotherapeutic drugs. Therefore targeting STAT3 or CXCR4 could be a new therapeutic strategy of AML.</p>

Prognostic factors in solitary plasmacytoma / 中国肿瘤临床

Objective:To investigate the clinical features, treatment strategies, and relative prognostic factors in 66 patients with solitary plasmacytoma (SP). Methods:The data of 644 patients, who were diagnosed with pathologically proven plasmacytoma in Tianjin Medical University Cancer Institute and Hospital between June 2000 and October 2012, were collected. Sixty-six of these patients (10.25%) were evaluated as SP, including 45 solitary bone plasmacytoma (SBP) and 21 extramedullary plasmacytoma (EMP). Results:SBP and EMP were the two clinical subsets of SP revealing the location of the lesion. SBP mostly occurred in the axial skeleton, whereas EMP was most frequently observed in the upper respiratory tract. The differences among tumor size, serum M-protein, and serumβ2-microglobulin exhibited statistical significance. Conclusion:Large tumor size (≥5 cm), positive serum M-protein, and serumβ2-microglobulin were the factors that affected the prognosis of SBP patients. Radiotherapy and serumβ2-microglobulin>3.5 mg/L were the favorable prognostic factors for EMP patients.

Efficacy comparision of thalidomide for 132 cases of newly diagnosed multiple myeloma with or without extramedullary disease / 白血病·淋巴瘤

Objective To investigate the clinical efficiency and effects on prognosis of thalidomide for newly diagnosed multiple myeloma (MM) with or without extramedullary disease.Methods The clinical features and prognostic factors were retrospectively analyzed in 132 patients.Analyze the efficiency of thalidomide and its effects on prognosis of MM patients with or without extramedullary disease.Results The median age of 132 patients was 59 years (28-83 years),52 patients (39.4 ％) had extramellulary multiple myeloma (EM),other 80 patients (60.6 ％) were without EM at diagnosis.The estimate overall survival (OS) of patients with EM was 42.5 months,compared with 54.3 months in those without EM,the difference was statistically significant (P =0.004).Patients accepting thalidomide therapy had a longer estimate OS than those without thalidomide therapy (50.7 months vs 41.2 months,P =0.01).For patients with EM,whether take thalidomide or not have no effect on the prognosis,the difference was not statistically significant (39.7 months vs 38.5 months,P =0.491).While for those without EM,the prognosis for patients who take thalidomide was better than that did not take thalidomide (54.6 months vs 41.2 months,P =0.027).Log-rank univariate analysis showed that accompanied with EM (P =0.004),the proportion of plasma cells≥20 ％ (P =0.02),Hb≤110 g/L (P =0.041),β2-MG ≥ 5.5 mg/L (P =0.018) and without thalidomide therapy (P =0.01) were poor prognostic factors.Multivariate analysis with COX model showed extramedullary disease,β2-MG and the proportion of plasma cells were statistically significant (P ＜ 0.05).Conclusion Patients with EM showed aggressive and complicated prognosis.Thalidomide does not improve the prognosis of patients with EM and they may need combination therapy such as bortezomib or autologous hemopoietic stem cell transplantation.