interphase-fluorescence-situ-hybridization-bone-marrow-smears

Interphase Fluorescence <em>in situ</em> Hybridization of Bone Marrow Smears of Multiple Myeloma

Fluorescence in situ hybridization (FISH) detection is an indispensable method in genetic risk stratification in multiple myeloma (MM), which is one of ...

zhongnan hospital of Wuhan University

MicroRNAs (miRNAs) are small, non-coding RNAs that play important roles in the carcinogenesis and progression of cancers. Aberrant expression of miRNAs in tissue and plasma has been found in various solid tumors. Our research aims to determine whether the abnormal plasma miRNA expression patterns can be used as a predictive marker for the diagnosis and prognosis of small cell lung cancer (SCLC). Fifty SCLC patients and 30 healthy controls annotated with clinical characteristics and specific questionnaire survey for smoking history were available. Quantification of several miRNAs (miR-20a-5p, miR-92a-2-5p and miR-17-5p) was performed using quantitative real-time polymerase chain reaction (qRT-PCR), and results were analyzed using SPSS statistics 17.0. Plasma miR-92a-2 level was significantly higher in the SCLC patients group compared with healthy control (P< 0.0001), the receiver operating characteristic (ROC) curve analysis showed that the specificity and sensitivity were at 100% and 56% for diagnosis of SCLC, area under the ROC curve (AUC) was 0.761. No other statistically significant differences were found in the expression level of plasma miR-92a-2 among survival analysis in SCLC. Detection of miR-92a-2 levels in plasma could be a potential and noninvasive method for the diagnosis of SCLC.

Plasma miR-92a-2 as a biomarker for small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the most malignant cancers in the world. Early diagnosis of NSCLC has become especially important for patient treatment and prognosis. Increasing evidence suggest that long non-coding RNA GAS5 plays vital roles in cancer proliferation and differentiation in NSCLC. However, its clinical value in the diagnosis of NSCLC is unclear. The objective of this study was to evaluate the importance of circulating GAS5 as a biomarker for NSCLC diagnosis. In our study, quantitative real-time PCR (QRT-PCR) was applied to detect the GAS5 expression level in 80 pairs of cancer tissues and 57 pairs of plasma samples of NSCLC patients. Further analysis was performed to study the differential expression of circulating GAS5 in 111 NSCLC patients and 78 healthy controls in our study. The results showed that GAS5 decreased in NSCLC tissues compared to noncancerous tissues (P<0.001). Furthermore, the GAS5 expression level was statistically declined in early stage of NSCLC before surgery compared with healthy controls (P<0.05) and sharply increased in postoperative groups (P=0.026). ROC curve analysis for early stage of NSCLC with the combination of GAS5, CEA and CA199 showed that the area under the ROC curve (AUC) was 0.734 (95% CI, 0.628‑0.839; P<0.0005). In conclusion, circulating GAS5 could be functioned as a potential combined biomarker for screening NSCLC and patient monitoring after surgical treatment.

Identification of circulating long non-coding RNA GAS5 as a potential biomarker for non-small cell lung cancer diagnosisnon-small cell lung cancer, long non-coding RNA, plasma, GAS5, biomarker.

Acute lymphoblastic leukemia (ALL) affects both children and adults. However, the prognosis of the two cohorts is quite different. The present aim was to review and evaluate one potential cause of why survival is poorer in adult ALL than pediatric ALL via fluorescence  hybridization (FISH). Clinical significant features were analyzed in 282 ALL cases. FISH was performed to study mixed lineage leukemia () translocation and the Philadelphia (Ph) chromosome in newly diagnosed patients, and was used to detect trisomy 4 or 10 and the translocation ETS leukemia-acute myeloid leukemia 1 () fusion gene. The overall survival/event-free survival (OS/EFS) outcome of adult ALL and pediatric ALL was analyzed using Kaplan-Meier analysis. Adult ALL had a higher median leukocyte count and lower hemoglobin level than pediatric ALL. FISH revealed that Ph positivity (Ph+) was associated with the high-risk feature of older age. In pediatric ALL, trisomy 4 or 10 was present in 71/207 cases (34.3%), while the  fusion gene was present in 16/207 cases (7.7%). By contrast, there were very few such positive cases in adult ALL. Survival analysis revealed that, in adult ALL, the 3-year OS and EFS rates were higher in the Ph-negative group than in the Ph+ group. Adult or pediatric ALL is an independent prognostic factor of OS. The present analysis of the clinical and biological features between adult and pediatric ALL indicates that adult ALL has a poorer prognosis than pediatric ALL based on Ph+ status and presence of trisomy 4 or 10. Ph+ ALL is an independent prognosis factor of ALL. FISH may serve an important role in the comparison of prognostic factors in adult and pediatric ALL.

Fluorescence  hybridization comparison of the prognostic factors in adult and pediatric acute lymphoblastic leukemia: A retrospective analysis of 282 cases.

Hepatocellular carcinoma (HCC) is one of the most malignant cancer with high morbidity and mortality which lead to a serious burden to society. AFP (alpha-fetoprotein) is the most widely used serum biomarker to detect HCC worldwide. However, no AFP elevation have been found in many HCC and AFP analysis can't be used to screen HCC in these cases. Currently, many studies have been carried out to find reliable biomarker in diagnosing AFP-negative HCC. Such biomarker would help the diagnosis of AFP-negative HCC, ensuring the timely initiation of treatment. In this review, we highlight the important role of biomarkers that can differentiate AFP-negative HCCs, and discuss their potential clinical applications as biomarkers for the diagnosis of AFP-negative HCC.

Current Status and Perspective Biomarkers in AFP Negative HCC: Towards Screening for and Diagnosing Hepatocellular Carcinoma at an Earlier Stage.

Integrating the proportion of ring sideroblasts and SF3B1 mutation status is required for diagnosis of sideroblastic subgroups in myelodysplastic syndrome (MDS) as proposed by the World Health Organization 2016 classification. However, the clinical implications of SF3B1 mutation and ring sideroblasts in MDS-refractory cytopenia with multilineage dysplasia (MDS-RCMD) remain unclear.

SF3B1 Mutation but Not Ring Sideroblasts Identifies a Specific Group of Myelodysplastic Syndrome-Refractory Cytopenia With Multilineage Dysplasia.

Myelodysplastic syndromes (MDS) are characterised by impaired haematopoiesis and a high risk of leukaemic transformation. A decrease in RPS14 expression in non-5q MDS patients was confirmed by immunohistochemical analyses of MDS bone marrow biopsies. To determine the cause of RPS14 reduction in non-5q MDS, we analysed the 3'-UTR of RPS14 and demonstrated that miR-223 binds to the 3'-UTR of RPS14 by bioinformatics-based approach combined with the luciferase reporter assay. Using quantitative real-time polymerase chain reaction (qRT-PCR) analysis, we observed a significantly increased expression of miR-223 in CD34+ cells and SKM-1 cells derived from non-5q MDS patients in vitro and demonstrated a correlation between miR-223 levels and red blood cell counts. Exogenous miR-223 expression in SKM-1 cells could also inhibit RPS14 expression. In functional studies, overexpression of miR-223 was shown to promote cell proliferation and inhibit cell apoptosis in SKM-1 cells, and to impair erythroid differentiation in haemin-induced K562 cells. Taken together, our results revealed that the overexpression of miR-223 in MDS is closely associated with cell transformation and erythroid differentiation arrest, which is most likely mediated by targeting RPS14.

The effect of miR-223 on cellular behaviour in non-5q myelodysplastic syndromes through targeting RPS14.

. The outbreak of COVID-19 has attracted the attention of the whole world. Our study aimed to describe illness progression and risk profiles for mortality in non-survivors. . We retrospectively analyzed 155 patients with COVID-19 in Wuhan and focused on 18 non-survivors among them. Briefly, we compared the dynamic profile of biochemical and immune parameters and drew an epidemiological and clinical picture of disease progression from disease onset to death in non-survivors. The survival status of the cohort was indicated by a Kaplan-Meier curve. . Of the non-survivors, the median age was 73.5 years, and the proportion of males was 72.2%. Five and 13 patients were hospital-acquired and community-acquired infection of SARS-CoV-2, respectively. The interval between disease onset and diagnosis was 8.5 days (IQR, [4-11]). With the deterioration of disease, most patients experienced consecutive changes in biochemical parameters, including lymphopenia, leukocytosis, thrombocytopenia, hypoproteinemia, as well as elevated D-dimer and procalcitonin. Regarding the immune dysregulation, patients exhibited significantly decreased T lymphocytes in the peripheral blood, including CD3T, CD3CD4Th, and CD3CD8Tc cells. By the end of the disease, most patients suffered from severe complications, including ARDS (17/18; 94.4%), acute cardiac injury (10/18; 55.6%), acute kidney injury (7/18; 38.9%), shock (6/18; 33.3%), gastrointestinal bleeding (1/18; 5.6%), as well as perforation of intestine (1/18; 5.6%). All patients died within 45 days after the initial hospital admission with a median survivor time of 13.5 days (IQR, 8-17). . Our data show that patients experienced consecutive changes in biochemical and immune parameters with the deterioration of the disease, indicating the necessity of early intervention.

Novel Insights Into Illness Progression and Risk Profiles for Mortality in Non-survivors of COVID-19.

A pandemic designated as Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. Up to date, there is no efficient biomarker for the timely prediction of the disease progression in patients. To analyze the inflammatory profiles of COVID-19 patients and demonstrate their implications for the illness progression of COVID-19. Retrospective analysis of 3,265 confirmed COVID-19 cases hospitalized between 10 January 2020, and 26 March 2020 in three medical centers in Wuhan, China. Patients were diagnosed as COVID-19 and hospitalized in Leishenshan Hospital, Zhongnan Hospital of Wuhan University and The Seventh Hospital of Wuhan, China. Univariable and multivariable logistic regression models were used to determine the possible risk factors for disease progression. Moreover, cutoff values, the sensitivity and specificity of inflammatory parameters for disease progression were determined by MedCalc Version 19.2.0. Age (95%CI, 1.017 to 1.048;  < 0.001), serum amyloid A protein (SAA) (95%CI, 1.216 to 1.396;  < 0.001) and erythrocyte sedimentation rate (ESR) (95%CI, 1.006 to 1.045;  < 0.001) were likely the risk factors for the disease progression. The Area under the curve (AUC) of SAA for the progression of COVID-19 was 0.923, with the best predictive cutoff value of SAA of 12.4 mg/L, with a sensitivity of 83.9% and a specificity of 97.67%. SAA-containing parameters are novel promising ones for predicting disease progression in COVID-19.

Novel biomarkers for the prediction of COVID-19 progression a retrospective, multi-center cohort study.

 Overexpression of vascular endothelial growth factor (VEGF), a major angiogenic factor, was found in myelodysplastic syndromes (MDS) and showed different expression statuses in different risk groups of MDS. We aimed to investigate the possible role of microRNA (miR)-15a and miR-16 on the regulation of VEGF expression and their effect on angiogenesis in lower- and higher-risk MDS.  We studied peripheral blood and bone marrow samples of MDS patients or several leukaemia and MDS cell lines by enzyme-linked immunosorbent assay, immunohistochemical staining, immunofluorescence and quantitative PCR for expression levels of VEGF, miR-15a and miR-16. MiRNA transfection and Luciferase reporter assays were conducted to investigate whether VEGF is a target of miR-16. Migration and tube formation assays were performed in cells exposed to medium from cells with overexpressed or knockdown miR-16.  It showed a significantly lower level of miR-16 in higher-risk MDS patients, while the VEGF levels were upregulated. Inverse correlation between VEGF and miR-16 were determined in cells lines including SKM-1, THP-1, and K562 cells. Overexpression of miR-16 in SKM-1 cells resulted in reduced VEGF secretion and cell protein levels. Direct binding of miR-16 to the 3' untranslated region (3'-UTR) of VEGF was confirmed by luciferase reporter assays. The migration and tube formation of human umbilical vein endothelial cells decreased in the presence of medium from SKM-1 cells with overexpressed miR-16.  These data suggest that miR-16 may play a role in angiogenesis in higher-risk MDS by targeting VEGF and therefore modulating MDS progression. MiR-16 might be a novel therapeutic target in higher-risk MDS.

Yalan Yu

Department of Hematology

zhongnan hospital of Wuhan University

Interphase Fluorescence in situ Hybridization of Bone Marrow Smears of Multiple Myeloma

Yalan Yu

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Hematology

zhongnan hospital of Wuhan University

Interphase Fluorescence in situ Hybridization of Bone Marrow Smears of Multiple Myeloma

Department of Hematology