Expression of miR-34a in Bone Marrow of Adult Acute Lymphoblastic Leukemia and Its Significance in Cell Drug Resistance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the expressions of miR-34a in bone marrow of adult acute lymphoblastic leukemia (ALL) and its relationship with drug resistance.</p><p><b>METHODS</b>Forty-seven cases of newly diagnosed adult ALL were selected and their bone marrow samples were taken at the time of newly diagnosed and relapsed or complete remission; 26 pairs of specimens were in newly diagnosed-complete remission group, and 21 pairs of specimens were in newly diagnosed-relapse group. The expressions of miR-34a in bone marrow samples, CCRF-CEM cells and resistant CEM-C1 cell strains were detected by real-time quantitative PCR. The expression of miR-34a in CCRF-CEM cells was inhibited and was increased in CEM-C1 cells detected by electroporation transfection method. All the cells were incubated at different concentration of camptothecin. The cell survival was analyzed by CCK-8 method, the cell proliferation inhibition rate (%) and resistance index (RI) were calculated.</p><p><b>RESULTS</b>In newly diagnosed-complete remission group, the miR-34a expression at newly diagnosis was significantly lower than that in complete remission and the control group, the differences were statistically significant (P < 0.05). In newly diagnosed-relapsed group, the miR-34a expressions at newly diagnosis and relapse were lower than those in the control group, the differences were statistically significant (P < 0.05). The expression level in CEM-C1 cells was (2.64 ± 1.37) which significantly lower than that in CCRF-CEM cells (5.14 ± 2.06), the differences were statistically significant (P < 0.05). The expression level of miR-34a in CCRF-CEM cells transfected with miR-34a inhibitor was (3.14 ± 1.15), which significantly lower than that in the miRNA inhibitor-negative control group, the difference was statistically significant (P < 0.05). The cell proliferation inhibition rate of CCRF-CEM cells transfected with miR-34a inhibitor was significantly higher than that in the negative control transfectedcells (P < 0.05), the IC(50) was 28.73 ng/mL and 2167.00 ng/mL respectively, and RI = 75.43. The expression level of miR-34a in CEM-C1 cells transfected with miR-34a mimic was (5.06 ± 1.73), which was significantly higher than that in the miRNA mimics transteted-negative control CEM-C1 cells (P < 0.05). The proliferation inhibition rate in CEM-C1 cells transfected with miR-34a mimic was significantly lower than that in the negative control-transfected cells (P < 0.05). The IC(50) was 112.57 ng/mL and 1.27 ng/mL respectively, and the RI = 88.64.</p><p><b>CONCLUSION</b>The expression of miR-34a in bone marrow samples of adult ALL is low which may be associated with the relapse and drug resistance of ALL.</p>

Chromophobe renal cell carcinoma: a clinicopathologic study and immunophenotypes of 42 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunohistochemical profiles and prognosis of chromophobe renal cell carcinoma (ChRCC).</p><p><b>METHODS</b>Forty-two cases of ChRCC were retrieved from the archival files of the Affiliated Hospital of Qingdao University, 401 Hospital of PLA and Qingdao Municipal Hospital from 2003 to 2011. The clinical and pathologic features of the tumors were reviewed. Hale colloidal iron staining was performed and EnVision immunohistochemistry was used to detect the expression of a series of immunologic markers. Forty cases of clear cell renal cell carcinoma and 10 cases of renal oncocytoma were selected as controls.</p><p><b>RESULTS</b>The patients included 17 males and 25 females. The age of patients ranged from 39 years to 78 years (median age = 57 years). On gross examination, the tumors ranged from 2 cm to 19 cm in greatest dimension (mean size = 7.3 cm). Histologically, the tumors were mainly composed of solid sheets, acini or tubules of malignant cells. The tumor cells contained clear finely reticular ("chromophobe") and eosinophilic cytoplasm with perinuclear clearing. The nuclear outline was irregular and wrinkled. Nucleoli were inconspicuous and mitotic figures were barely seen. Hale colloidal iron stain was positive in all cases. Immunohistochemically, the tumor cells were variably positive for EMA (100%, 42/42), CK7 (95.2%, 40/42), Ksp-cad (92.9%, 39/42), CK18 (88.1%, 37/42), CD117 (61.9, 26/42), CD10 (31.0%, 13/42) and PAX2 (28.6%, 12/42). They were negative for vimentin, CA IX and TFE3. The follow-up period in 31 patients ranged from 2 to 77 months (average duration = 29 months). Three patients died of tumor metastasis 3, 8, 13 months respectively after the operation. Twenty-eight patients were still alive without evidence of tumor recurrence.</p><p><b>CONCLUSIONS</b>ChRCC predominantly occurs in middle-aged and elderly patients. It often carries a favorable prognosis. The presence of plant cell-like morphology, pale cells with uniform reticular microvesicular appearance and perinuclear clearing are characteristic histologic features. The diffuse positivity for Hale colloidal iron stain and EMA/CK7/Ksp-cadherin/CD117-positive immunoprofiles are also useful in differential diagnosis.</p>