Expression Profiles in Chronic Lymphoid Leukemia by Hematochip Analysis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4676-4676
Author(s):  
Patricia Alvarez ◽  
Virginia Leon ◽  
Gonzalo Caballero ◽  
Araceli Rubio-Martinez ◽  
Miguel Pocovi ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Expression Profiles ◽  
Statistical Significance ◽  
University Hospital ◽  
High Yield ◽  
Genetic Profile ◽  
Lymphoid Leukemia ◽  
Chronic Lymphoid Leukemia ◽  
Response Predictors ◽  
Mutational Status

Abstract Aim: The gene expression analysis system is a good tool to identify biomarkers related to prognosis or response predictors of therapy in haematological malignancies. Low density microarrays are an useful technology to obtain genetic expression profiles in different neoplastic disorders. Recently we have designed an oligonucleotide biochip (Hematochip, Alvarez et al, Clin Chem2007;53:259) useful for study peripheral blood in hematological malignancies. Chronic Lymphoid Leukemia (CLL) is a frequent clonal lymphocyte disorder characterized by clinical diversity and that have known prognosis markers but a more accurate subclassification could be required. Our objective was to define CLL subgroups with differential genetic profile expression. Patients and Methods: Analytical, prospective study in 49 consecutive CLL patients diagnosed since January 2003 to December 2004 in the Hematology Department of Miguel Servet University Hospital. Zaragoza. Spain. At diagnosis demographic, clinical stage, analytical, immunophenotype expression, genetic aberrations and mutational status of IgVH were collected at electronically data base. Simultaneously, peripheral blood from 20 healthy donors and all CLL patients were collected in PAXgene tubes (PreAnalytix). cDNA was generated from total RNA and double-strand cDNA was used as a template to generate biotinylated cRNA by in vitro transcription using the MEGA-script T7 High Yield Transcription kit (Ambion). Fragmented cRNA was denatured and hybridized using a Ventana Discovery Station (Ventana Medical Systems). Arrays were stained with Cy3-conjugated streptavidin (Amersham Biosciences) and scanned using a ScanArray 4000 scanner (Perkin-Elmer). The data were treated and analyzed by GeneSpring clusters method. The expression profiles were compared and stratified with clinical stability or progression, gender, ZAP 70 expression, associated neoplasia, time free of therapy and response or not to Fludarabine. Results: The Hematochip has identified 9 probes obtained with filtered data and statistical significance (p<0.01), related to stable or progressive disease. The results had been validated by RT-PCR. Comments: the study of genetic profiles by Hematochip could be a useful analysis to predict the stability or progression of CLL patients at diagnosis. Further studies analyzing more cases will be necessary in order to validate these results. This work has been partially sponsorized by grants: Mutua Madrilena del Automovil, Fundacion para el Estudio de la Hematologia y Hemoterapia de Aragon and I+CS.

scholarly journals Deregulated Genes in Hematopoietic Stem Cells Isolated from Spleen of Patients with Myelofibrosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4279-4279
Author(s):  
Paolo Catarsi ◽  
Francesca Cordero ◽  
Giulio Ferrero ◽  
Marco Beccuti ◽  
Valentina Poletto ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Stem Cell Differentiation ◽  
Hematopoietic Stem ◽  
Mutational Status ◽  
Cd34 Cells ◽  
Upregulated Genes

Abstract An important issue in myeloproliferative diseases research is to test the hypothesis that in the neo-angiogenesis, which is observed in the spleen and bone marrow of patients, involves endothelial cells derived from the neoplastic clone. In this study we analyzed the gene expression profile of 138 genes in CD34+ hematopoietic cells from the spleen and peripheral blood of patients with myelofibrosis (MF) and healthy individuals (HI). These genes have been selected among those that characterize the neoangiogenic gene signature or belonging to deregulated expression pathways in MF, and are listed in Table1. By using quantitative reverse transcription-PCR (RT-qPCR), we measured the expression levels of 141 targets and 5 reference genes in CD34+ cells isolated by immunomagnetic method from the spleen and peripheral blood of 4 patients and 3 HI. For calculation of the statistical significance of the differences we used the t-test for unpaired samples. A p<0.05 was considered to be statistically significant. All data analyses were performed with GenEx (version 6.1, MultiD). To characterize the differentially expressed genes obtained in each comparison, the lists of genes were analyzed through several tools, i.e. String, Enrichr and GSEA analysis. The comparison between spleen CD34+ cells and circulating CD34+ cells reveal a group of common genes in both patients and heathy donors. Those genes are significantly overexpressed in spleen. Some of the common genes are involved in the regulation of cell migration and in the development of blood vessels were significantly overexpressed in splenic CD34+ cells compared to circulating CD34+ cells. However, we observed that many of the genes implicated in the development of the vessels were under-expressed in CD34+ cells isolated from the spleen of patients compared to those of HI. The most significant upregulated genes in CD34+ splenic cells from patients included transcripts (GATA1, HBB, TAL1, GATA2, PTGS1) belonging to the molecular signature of CD34+ cells isolated from the bone marrow (BM) of patients with chronic myeloid leukemia (Diaz-Blanco E. et al., Leukemia 2007). Another group of upregulated genes (GATA1, TAL1, ITGB3, GATA2, PF4) are also identified in a study designed to characterize the genes essential to the development of megakaryocytes (Tenedini et al. Blood 2004). These two groups of genes are part of an expression pattern characteristic for immature stem cells as well as megakaryocyte-erythrocyte progenitor cells. Another group of genes overexpressed in patients spleens (CD34, ANGPT1, PF4, GATA2, PTGS1), which includes some of the above mentioned genes, has been observed in a comparison between circulating CD34+ cells from patients with myelofibrosis, and CD34 + cells isolated from the bone marrow of HI (Guglielmelli P. et al. Stem Cells 2007). Among the underexpressed genes in the spleen of patients we mention CXCR4, in keeping with previous observations. Interestingly, among the aforementioned genes, GATA1 and GATA2 genes are overexpressed in granulocytes of patients with MPNs regardless of the JAK2/CALR mutational status whereas PTGS1 is overexpressed in the JAK2-V617F homozygous and CALR-mutated granulocytes (Rampal et al. Blood 2014). We focused our attention on PTGS1 because its well-known activity in regulating angiogenesis, which can be inhibited in vitro by treatment with aspirin (Tsujii, M. et al. Cell 1998). To explain the mechanism of action of low-doses aspirin in this context, it has been proposed a model that involves permanent inactivation of PTGS1 in platelets. Indeed, PTGS1 is the only cyclooxygenase isoenzyme present in platelets. Moreover, Dixon and colleagues (Dixon, D.A. et al. JCI 2006), demonstrated that activated platelets induced the expression of PTGS2 in monocytes. It is believed that the synthesis of prostaglandin E2 by PTGS2 in tissues, is linked to an increment of angiogenesis and cell proliferation, and to a reduction of apoptosis. According to this concept, our data point toward a model in which, in the spleen of patients with MF, an altered hematopoietic stem cell differentiation could induce an inflammation-mediated angiogenesis through the overexpression of PTGS1 and a consequent induction of PTGS2 in cells of the splenic microenvironment. Table Table. Disclosures No relevant conflicts of interest to declare.

scholarly journals Characteristics of CD11c+CD5+ chronic B-cell leukemias and the identification of novel peripheral blood B-cell subsets with chronic lymphoid leukemia immunophenotypes [see comments]

Blood ◽  
1990 ◽  
Vol 76 (1) ◽  
pp. 123-130 ◽  
Author(s):  
SB Wormsley ◽  
SM Baird ◽  
N Gadol ◽  
KR Rai ◽  
RE Sobol
Keyword(s):  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Small Lymphocyte ◽  
Lymphoid Leukemia ◽  
Color Flow ◽  
Prolymphocytic Leukemia ◽  
Normal Peripheral Blood ◽  
Chronic Lymphoid Leukemia ◽  
B Cell Subsets

Previous studies have indicated that chronic lymphocytic leukemias (CLL) are characterized by the coexpression of CD5 and B-cell antigens, while hairy cell leukemias (HCL) typically express CD11c+CD5- B-cell immunophenotypes. In this report we describe the features of B-cell leukemias with CD11c+CD5+ immunophenotypes and the identification of novel circulating B-cell subsets defined by the expression of CD20, CD5, and CD11c antigens. Morphologic evaluation of 14CD11c+CD5+ B-cell leukemias showed that they generally had larger cellular diameters (14 to 21 microns) and lower nuclear:cytoplasm ratios than typical small lymphocyte CLL. These cases did not exhibit the well-defined nucleoli characteristic of prolymphocytic leukemia (PLL). The presenting clinical features of CD11c+CD5+ B-cell leukemias were most consistent with CLL or PLL, and none of the evaluated cases had pancytopenia, splenomegaly, and cytoplasmic villi characteristic of HCL. Examination of normal peripheral blood (n = 6) by three-color flow cytometry identified four novel B-cell subsets with the following immunophenotypes (mean percent of total CD20+ B cells +/- SE): CD20+CD5+CD11c+ (8.0 +/- 1.6); CD20+CD5-CD11c+ (12.0 +/- 2.0); CD20+CD5+CD11c- (35.0 +/- 4.9); and CD20+CD5-CD11c- (44.0 +/- 5.0). Our findings suggest that CD11c+CD5+ B-cell leukemias with atypical morphologic features represent forms of CLL or PLL rather than HCL. In addition, we have identified novel subsets of circulating B cells defined by patterns of CD20, CD5, and CD11c expression that correspond to the immunophenotypes of chronic B-cell leukemias.

Gene Expression in CLL Cells Associated with Lymphadenopathy and Chromosome 11q23 Deletion.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 971-971
Author(s):  
John D. Dickinson ◽  
Avadhut Joshi ◽  
Jamie Gilmore ◽  
Philip J. Bierman ◽  
Sanger Warren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Signaling ◽  
Differentially Expressed Genes ◽  
Peripheral Blood ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Mediastinal Lymphadenopathy ◽  
Fibroblast Growth Factor 21 ◽  
Mutational Status

Abstract Previously we have demonstrated that peripheral blood samples with B-cell Chronic Lymphocytic Leukemia (CLL) have different gene expression profiles associated with chromosome aberrations detected by fluorescence in situ hybridization (FISH). In particular, the vast majority of differentially expressed genes were related to the presence of the 11q23 deletion. The 11q23 deletion has previously been shown to be correlated with shortened over-all survival and extensive/bulky lymphadenopathy. In this study we sought to identify genes whose expression may play role in the progression of CLL in patients that carry the 11q23 deletion. Gene expression from 10,700 human gene specific 50-mer oligos (MWG Biotech, Ebersberg, Germany) was compared between two groups of peripheral blood CLL samples. The first group consisted of CLL patients with the 11q23 deletion detected by FISH as well as with the presence of abdominal/mediastinal lymphadenopathy. The second group consisted of CLL patients without the 11q23 deletion and without the presence of known abdominal/mediastinal lymphadenopathy. The non-11q deletion group included CLL patients with the 13q14 deletion, trisomy 12, 17p13 deletion, as well as several without any detectable abnormality. Immunoglobulin heavy chain variable region (IgVH) mutational status was compared in CLL samples in both groups to ensure that resulting expression differences were not the result of this known prognostic marker. Median of ratios was compared between the two groups. Eighty-eight (87) genes had a p-value < 0.01. Gene function was classified at the European Molecular Biology Laboratory (EMBL) Bioinformatic Harvester website. Twenty of these differentially expressed genes were cell cycle/cell signaling related genes that were over-expressed in the 11q23 deletion group. Examples include: activating transcription factor 4, rho-associated coiled-coil containing protein kinase 2, fibroblast growth factor 21 precursor, signal transducing adaptor molecule 1, mad2-like 1, interferon receptor 1, pim-2 oncogene, and zw10 interactor. In comparison, using the same peripheral blood CLL samples, 78 genes were differentially expressed (p < 0.01) between those samples that had a mutated IgVH versus those that had an unmutated IgVH. Therefore, the presence of both the 11q23 deletion and bulky abdominal/mediastinal lymphadenopathy significantly alters the gene expression profile of peripheral blood CLL cells, particularly genes related to the cell cycle and cell signaling related processes. Biological roles of some of these genes may help further elucidate the basis of the clinical behavior of CLL patients

scholarly journals Characteristics of CD11c+CD5+ chronic B-cell leukemias and the identification of novel peripheral blood B-cell subsets with chronic lymphoid leukemia immunophenotypes [see comments]

Blood ◽  
1990 ◽  
Vol 76 (1) ◽  
pp. 123-130 ◽  
Author(s):  
SB Wormsley ◽  
SM Baird ◽  
N Gadol ◽  
KR Rai ◽  
RE Sobol
Keyword(s):  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Small Lymphocyte ◽  
Lymphoid Leukemia ◽  
Color Flow ◽  
Prolymphocytic Leukemia ◽  
Normal Peripheral Blood ◽  
Chronic Lymphoid Leukemia ◽  
B Cell Subsets

Abstract Previous studies have indicated that chronic lymphocytic leukemias (CLL) are characterized by the coexpression of CD5 and B-cell antigens, while hairy cell leukemias (HCL) typically express CD11c+CD5- B-cell immunophenotypes. In this report we describe the features of B-cell leukemias with CD11c+CD5+ immunophenotypes and the identification of novel circulating B-cell subsets defined by the expression of CD20, CD5, and CD11c antigens. Morphologic evaluation of 14CD11c+CD5+ B-cell leukemias showed that they generally had larger cellular diameters (14 to 21 microns) and lower nuclear:cytoplasm ratios than typical small lymphocyte CLL. These cases did not exhibit the well-defined nucleoli characteristic of prolymphocytic leukemia (PLL). The presenting clinical features of CD11c+CD5+ B-cell leukemias were most consistent with CLL or PLL, and none of the evaluated cases had pancytopenia, splenomegaly, and cytoplasmic villi characteristic of HCL. Examination of normal peripheral blood (n = 6) by three-color flow cytometry identified four novel B-cell subsets with the following immunophenotypes (mean percent of total CD20+ B cells +/- SE): CD20+CD5+CD11c+ (8.0 +/- 1.6); CD20+CD5-CD11c+ (12.0 +/- 2.0); CD20+CD5+CD11c- (35.0 +/- 4.9); and CD20+CD5-CD11c- (44.0 +/- 5.0). Our findings suggest that CD11c+CD5+ B-cell leukemias with atypical morphologic features represent forms of CLL or PLL rather than HCL. In addition, we have identified novel subsets of circulating B cells defined by patterns of CD20, CD5, and CD11c expression that correspond to the immunophenotypes of chronic B-cell leukemias.

P0203EARLY DETECTION OF BREAST ARTERIAL CALCIFICATION IN DIFFERENT STAGES OF CHRONIC KIDNEY DISEASE PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Basma Sultan ◽  
Hamdy Omar ◽  
Housseini Ahmed ◽  
Mahmoud Elprince ◽  
Osama Anter adly ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Lipid Profile ◽  
Statistical Significance ◽  
University Hospital ◽  
Arterial Calcification ◽  
Control Group ◽  
Inpatient Ward ◽  
Stage 4 ◽  
Ckd Stage

Abstract Background and Aims Vascular calcification (VC) plays a major role in cardiovascular disease (CVD), which is one of the main causes of mortality in patients with chronic kidney disease (CKD). The study aims at early detection of breast arterial calcification (BAC) in different stages of CKD (stage 2, 3& 4) patients as an indicator of systemic VC. Method A case control study was conducted targeting CKD women, aged 18- 60 years old. The sample was divided into 3 groups; A,B,C (representing stage 2, 3 & 4 of CKD) from women who attended nephrology and Internal medicine clinics and admitted in inpatient ward in Suez Canal University Hospital. A 4th group (D) was formed as a control group and included women with normal kidney functions (each group (A, B, C, D) include 22 women). The selected participants were subjected to history taking, mammogram to detect BAC and biochemical assessment of lipid profile, Serum creatinine (Cr), Mg, P, Ca, PTH and FGF23. Results Our study detected presence of BAC in about 81.8% of hypertensive stage 4 CKD patients compared with 50% in stage 3 CKD, also in the majority of stage 4 CKD patients who had abnormal lipid profile parameters and electrolyte disturbance. Most of the variables had statistical significance regarding the presence of BAC. Conclusion Although it is difficult to determine the definite stage at which the risk of VC begins but in our study, it began late in stage 2 CKD, gradually increased prevalence through stage 3 and became significantly higher in stage 4. These results suggest that preventive strategies may need to begin as early as stage 2 CKD.

scholarly journals Cost Effectiveness of Transbronchial Needle Aspiration

1999 ◽  
Vol 6 (4) ◽  
pp. 332-335 ◽  
Author(s):  
Jennifer A Crocket ◽  
Eric YL Wong ◽  
Dale C Lien ◽  
Khanh Gia Nguyen ◽  
Michelle R Chaput ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Cost Effective ◽  
Diagnostic Procedures ◽  
Needle Aspiration ◽  
Benign Disease ◽  
University Hospital ◽  
High Yield ◽  
Transbronchial Needle Aspiration ◽  
Computed Tomographic ◽  
The Cost

OBJECTIVE: To evaluate the yield and cost effectiveness of transbronchial needle aspiration (TBNA) in the assessment of mediastinal and/or hilar lymphadenopathy.DESIGN: Retrospective study.SETTING: A university hospital.POPULATION STUDIED: Ninety-six patients referred for bronchoscopy with computed tomographic evidence of significant mediastinal or hilar adenopathy.RESULTS: Ninety-nine patient records were reviewed. Three patients had two separate bronchoscopy procedures. TBNA was positive in 42 patients (44%) and negative in 54 patients. Of the 42 patients with a positive aspirate, 40 had malignant cytology and two had cells consistent with benign disease. The positive TBNA result altered management in 22 of 40 patients with malignant disease and one of two patients with benign disease, thereby avoiding further diagnostic procedures. The cost of these subsequent procedures was estimated at $27,335. No complications related to TBNA were documented.CONCLUSIONS: TBNA is a high-yield, safe and cost effective procedure for the diagnosis and staging of bronchogenic cancer.

scholarly journals POS1281 HOW DOES OBESITY INFLUENCE THE FEATURES OF KNEE OSTEOARTHRITIS?

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 923.4-924
Author(s):  
H. Hachfi ◽  
D. Khalifa ◽  
M. Brahem ◽  
N. Ben Chekaya ◽  
M. Younes
Keyword(s):  
Knee Osteoarthritis ◽  
Functional Impairment ◽  
Statistical Significance ◽  
Obese Group ◽  
University Hospital ◽  
Obese Patients ◽  
Cross Sectional ◽  
Duration Of Symptoms ◽  
Lequesne Index ◽  
The Mean

Background:Knee osteoarthritis and obesity are both major health problems. It is now admitted that the prevalence of knee osteoarthritis gets higher with obesity and that weight loss helps knee function and allows patients to avoid surgery.Objectives:The aim of this study was to study the influence of obesity on knee osteoarthritis features.Methods:A cross-sectional study was conducted in the university hospital Taher Sfar of Tunisia over a period of 6 months. Patients who had knee osteoarthritis confirmed by radiographs were included. Sociodemographic, clinical, radiological and therapeutic data were collected from medical records and visits. Obesity was defined by a body mass index (BMI) ≥30. Functional impairment was assessed by the Womac index and Lequesne index.Results:The study included 186 patients. There were 31 males and 155 femmes. The mean age was 60±10 years. The percentage of obese patients was 53,8%. The mean age was similar in both groups obese and non obese. There were more women in the obese group compared to the non obese group (p=0.0001), more patients who had diabetes mellitus and dyslipidemia (p=0.002). Non-obese patients had a shorter duration of symptoms with no statistical significance (p=0.151). Obese patients had more involvement of both knees (p<0.0001). Obesity did not have an impact on pain severity. Severity of radiological images (p=0,0001) were more frequent in obese patients. Functional impairment was similar in both groups. However, the percentage of patients having a very important functional impairment with Lequesne index was higher in obese patients (p<0.029). Obese patients also needed more physical therapy sessions (p=0.035).Conclusion:Knee osteoarthritis in obese patients is characterized with the femlae gender predominance, bilateral knee involvement, and a more severe images on radiographs. Thus the need for better control of weight and the importance of physical activity.References:[1]Coggon D, Reading I, Croft P, et al. Knee osteoarthritis and obesity. Int J Obes Relat Metab Disord J Int Assoc Study Obes 2001; 25: 622–627.Disclosure of Interests:None declared

scholarly journals Evaluation of Pregnancy Outcomes at Advanced Maternal Age

2019 ◽  
Vol 7 (12) ◽  
pp. 1951-1956 ◽  
Author(s):  
Małgorzata Radoń-Pokracka ◽  
Beata Adrianowicz ◽  
Magdalena Płonka ◽  
Paulina Danił ◽  
Magdalena Nowak ◽  
...  
Keyword(s):  
Caesarean Section ◽  
Gestational Age ◽  
Maternal Age ◽  
Statistical Significance ◽  
Advanced Maternal Age ◽  
Neonatal Outcomes ◽  
University Hospital ◽  
Large For Gestational Age ◽  
Predisposing Factor ◽  
Over 40 Years

AIM: The study aimed to investigate the association between advanced maternal age (AMA) and the risk of adverse maternal, perinatal and neonatal outcomes about parity in singleton pregnancies.METHODS: We retrospectively analysed 950 women who gave birth in the Department of Obstetrics and Perinatology of the University Hospital in Kraków for six months (between 1st January and 30th June 2018). The patients were divided into 3 groups according to their age (30-34 years old, 35-39 years old and over 40 years old). Each of these groups was subsequently subdivided into 2 groups depending on parity (primiparae and multiparae). Maternal, perinatal and neonatal outcomes were compared between the groups and the subgroups.RESULTS: Comparison of the three age groups revealed that advanced maternal age might constitute a predisposing factor for preterm birth, caesarean section and large for gestational age (LGA). From these parameters, statistical significance was reached in case of greater risk of LGA (OR = 2.17), caesarean section (OR = 2.03) and elective C-section (OR = 1.84) in women over 40 years old when compared to the patients aged 30-34. Furthermore, AMA increases the risk of postpartum haemorrhage (OR = 6.43). Additionally, there is a negative correlation between maternal age and gestational age at delivery (R = -0.106, p < 0.05).CONCLUSIONS: Advanced maternal age can undoubtedly be associated with several adverse perinatal outcomes. At the same time, the risk of perinatal complications begins to increase after the age of 35 but becomes significant in women aged ≥ 40.

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