scholarly journals Cyclin E overexpression in relapsed adult acute lymphoblastic leukemias of B-cell lineage

Blood ◽  
1996 ◽  
Vol 87 (8) ◽  
pp. 3360-3367 ◽  
Author(s):  
R Scuderi ◽  
KA Palucka ◽  
K Pokrovskaja ◽  
M Bjorkholm ◽  
KG Wiman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Lymphoblastic Leukemia ◽  
Cyclin E ◽  
Cell Lineage ◽  
Cyclin A ◽  
Mean Value ◽  
Peripheral Blood Mononuclear ◽  
Protein Levels

Using Western blot analysis, we examined cyclin E and cyclin A protein levels in 19 patients with acute lymphoblastic leukemia ([ALL] 15 B-ALL and four T-ALL). Whereas normal, nonproliferating peripheral blood mononuclear cells (PBMCs) expressed low levels of the 50-kD cyclin E, ALL blasts in the peripheral blood, although showing low-level or no proliferation as judged by FACS/cell-cycle analysis and cyclin A protein levels, expressed high levels of cyclin E, with a mean value similar to that of the proliferating Burkitt's lymphoma cell line, Akata. The accumulation of a protein shown to shorten the G1 phase of the cell cycle, cyclin E, in growth-delayed leukemic blasts may reflect the malignant status of these cells. Before treatment, B-ALL cells expressed predominantly the 50-kD cyclin E. T-ALL samples displayed the 50-kD cyclin E protein and a smaller, approximately 43-kD cyclin E species. In paired B-ALL samples taken before treatment and at relapse, we found a significant overexpression of the 50-kD protein in relapsed samples (P < .006), plus the presence of up to four additional smaller- molecular-weight species of cyclin E, illustrating clear diagnosis versus relapse differences. Cyclin E expression in ALL blasts may correlate to the relative malignant status of the cells, with higher protein levels reflecting a more advanced stage of the disease and a greater potential to proliferate under permissive conditions.

scholarly journals Peripheral Blood Mononuclear Cells Antioxidant Adaptations to Regular Physical Activity in Elderly People

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1555 ◽  
Author(s):  
Carla Busquets-Cortés ◽  
Xavier Capó ◽  
Maria Bibiloni ◽  
Miquel Martorell ◽  
Miguel Ferrer ◽  
...  
Keyword(s):  
Physical Activity ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Regular Physical Activity ◽  
Antioxidant Defenses ◽  
Active Lifestyle ◽  
Peripheral Blood Mononuclear ◽  
Protein Levels ◽  
Blood Mononuclear Cells

Regular physical activity prescription is a key point for healthy aging and chronic disease management and prevention. Our aim was to evaluate the antioxidant defense system and the mitochondrial status in peripheral blood mononuclear cells (PBMCs) and the level of oxidative damage in plasma in active, intermediate and inactive elderly. In total, 127 healthy men and women >55 years old participated in the study and were classified according on their level of declared physical activity. A more active lifestyle was accompanied by lower weight, fat mass and body mass index when compared to a more sedentary life-style. Active participants exhibited lower circulating PBMCs than inactive peers. Participants who reported higher levels of exercise had increased antioxidant protein levels when compared to more sedentary partakers. Carbonylated protein levels exhibited similar behavior, accompanied by a significant raise in expression of cytochrome c oxidase subunit IV in PBMCs. No significant changes were found in the activities of antioxidant enzymes and in the expression of structural (MitND5) and mitochondrial dynamic-related (PGC1α and Mitofusins1/2.) proteins. Active lifestyle and daily activities exert beneficial effects on body composition and it enhances the antioxidant defenses and oxidative metabolism capabilities in PBMCs from healthy elderly.

scholarly journals Co-infusion of high-dose haploidentical donor cells and CD19-targeted CART cells achieves complete remission, successful donor engraftment and significant CART amplification in advanced ALL

2020 ◽  
Vol 12 ◽  
pp. 175883592092760 ◽  
Author(s):  
Changlin Yu ◽  
Bo Cai ◽  
Yao Wang ◽  
Zhiqiang Wu ◽  
Kaixun Hu ◽  
...  
Keyword(s):  
Complete Remission ◽  
B Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Lymphoblastic Leukemia ◽  
Human Leukocyte ◽  
High Dose ◽  
Peripheral Blood Mononuclear ◽  
Grade Ii

Autologous CD19-targeted chimeric antigen receptor-modified T cells (CD19-CART) remarkably improved the outcome of patients with advanced B-cell acute lymphoblastic leukemia (B-ALL). However, the application and outcomes of allogeneic CART cells is still uncertain. Two patients with advanced B-ALL were enrolled to receive a co-infusion of high-dose human leukocyte antigen-haploidentical donor granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cells (GPBMCs; 21.01–25.34 × 108/kg) and the same donor-derived CD19-targeted CART cells (8.44–22.19 × 106/kg) without additional in vitro gene-editing following a reinduction chemotherapy as precondition. They achieved complete remission and full donor chimerism (FDC) with ongoing 20- and 4-month leukemia-free survival. A significant amplification of donor CART cells was detected in peripheral blood and/or cerebrospinal fluid and was associated with the formation of FDC. The highest amount of copies of the donor CART cells reached 4962 per µg of genomic DNA (gDNA) and 2449 per µg of gDNA, and the longest persistence was 20 months associated with B cell aplasia. Two patients experienced Grade II or III cytokine release syndromes and developed controllable Grade II intestinal acute graft-versus-host disease (GVHD) or limited chronic oral GVHD. High-dose donor GPBMC infusion may enhance amplification and persistence of haploidentical CD19-targeted CART cells, suggesting an alternative therapy for advanced B-ALL patients.

scholarly journals Selenoprotein T Promotes Proliferation and G1-to-S Transition in SK-N-SH Cells: Implications in Parkinson's Disease

2019 ◽  
Vol 149 (12) ◽  
pp. 2110-2119 ◽  
Author(s):  
Zi-Qiang Shao ◽  
Xiong Zhang ◽  
Hui-Hui Fan ◽  
Xiao-Shuang Wang ◽  
Hong-Mei Wu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Selenoprotein T ◽  
Blood Mononuclear Cells ◽  
6 Hydroxydopamine

ABSTRACT Background Selenium is prioritized to the brain mainly for selenoprotein expression. Selenoprotein T (SELENOT) protects dopaminergic, postmitotic neurons in a mouse model of Parkinson's disease (PD). Objective We hypothesized a proliferative role of SELENOT in neural cells. Methods To assess SELENOT status in PD, sedated male C57BL/6 mice at 10–12 wk of age were injected with 6-hydroxydopamine in neurons, and human peripheral blood mononuclear cells were isolated from 9 healthy subjects (56% men, 68-y-old) and 11 subjects with PD (64% men, 63-y-old). Dopaminergic neural progenitor–like SK-N-SH cells with transient SELENOT overexpression or knockdown were maintained in the presence or absence of the antioxidant N-acetyl-l-cysteine and the calcium channel blocker nimodipine. Cell cycle, proliferation, and signaling parameters were determined by immunoblotting, qPCR, and flow cytometry. Results SELENOT mRNA abundance was increased (P &lt; 0.05) in SK-N-SH cells treated with 1-methyl-4-phenylpyridinium iodide (3.5-fold) and peripheral blood mononuclear cells from PD patients (1.6-fold). Likewise, SELENOT was expressed in tyrosine hydroxylase–positive dopaminergic neurons of 6-hydroxydopamine–injected mice. Knockdown of SELENOT in SK-N-SH cells suppressed (54%; P &lt; 0.05) 5-ethynyl-2′-deoxyuridine incorporation but induced (17–47%; P &lt; 0.05) annexin V–positive cells, CASPASE-3 cleavage, and G1/S cell cycle arrest. SELENOT knockdown and overexpression increased (88–120%; P &lt; 0.05) and reduced (37–42%; P &lt; 0.05) both forkhead box O3 and p27, but reduced (51%; P &lt; 0.05) and increased (1.2-fold; P &lt; 0.05) cyclin-dependent kinase 4 protein abundance, respectively. These protein changes were diminished by nimodipine or N-acetyl-l-cysteine treatment (24 h) at steady-state levels. While the N-acetyl-l-cysteine treatment did not influence the reduction in the amount of calcium (13%; P &lt; 0.05) by SELENOT knockdown, the nimodipine treatment reversed the decreased amount of reactive oxygen species (33%; P &lt; 0.05) by SELENOT overexpression. Conclusions These cellular and mouse data link SELENOT to neural proliferation, expanding our understanding of selenium protection in PD.

scholarly journals miR-106a Is Downregulated in Peripheral Blood Mononuclear Cells of Chronic Hepatitis B and Associated with Enhanced Levels of Interleukin-8

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Zhongsi Hong ◽  
Haiyu Hong ◽  
Jian Liu ◽  
Xiaobin Zheng ◽  
Mingxing Huang ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Luciferase Activity ◽  
Peripheral Blood Mononuclear ◽  
Protein Levels ◽  
Qrt Pcr ◽  
Blood Mononuclear Cells

Aims. This study aimed to investigate miR-106a expression in peripheral blood mononuclear cells (PBMCs) of chronic hepatitis B (CHB) patients and to analyze the function of miR-106a.Materials and Methods. miR-106a expression levels in PBMCs from 40 healthy controls and 56 CHB patients were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The luciferase activity assays were used to determine whether miR-106a binds to 3′UTR of IL-8. miR-106a mimics and inhibitors were transfected into healthy PBMCs. IL-8 mRNA and protein levels were detected and determined by qRT-PCR and ELISA, respectively.Results. The qRT-PCR results suggested that the PBMC miR-106a levels were decreased in CHB patients. IL-8 was augmented in CHB patients and was inversely correlated with miR-106a levels. The luciferase activity assays indicated that IL-8 is a target of miR-106a. Exogenous expression of miR-106a could significantly repress IL-8 expression at both mRNA and protein levels in PBMCs, whereas miR-106a inhibitor had the opposite effects.Conclusions. This study suggested that miR-106a is downregulated in PBMCs of CHB patients and that miR-106a may play an important role in CHB by targeting IL-8.

scholarly journals Characterization of normal peripheral blood lymphocyte colony-forming cells: cell cycle status, surface markers, and cellular growth requirements

Blood ◽  
1983 ◽  
Vol 61 (3) ◽  
pp. 548-555
Author(s):  
R Taetle ◽  
D To ◽  
A Caviles ◽  
SW Norby ◽  
J Mendelsohn
Keyword(s):  
Cell Cycle ◽  
Peripheral Blood ◽  
B Lymphocyte ◽  
Mononuclear Cells ◽  
Optimal Growth ◽  
Colony Growth ◽  
Cellular Growth ◽  
Peripheral Blood Mononuclear ◽  
Normal Peripheral Blood ◽  
Cell Cycle Status

We performed a series of studies to further clarify the nature of lymphocyte colony-forming cells (CFC) from normal peripheral blood. Mononuclear cells were separated into E-rosette-enriched (E+) and E- rosette-depleted (E-) populations and cultured in methylcellulose with conditioned media and irradiated mononuclear cells. Linear plating relationships were obtained with plating efficiencies of 0.26% +/- .02% (mean +/- SE) for E+ CFC and 0.18% +/- .02% for E- CFC. Cells in E+ colonies were T lymphocytes and in E- colonies were B lymphocytes as determined by cell surface marker analysis. Using the thymidine suicide technique, approximately one-half of CFC were found to be in cycle at any moment, and plating efficiencies and cell cycle status of E+ CFC were not changed by preincubation with PHA in liquid culture for 48 hr. Using antibody complement-mediated cytotoxicity, E+ CFC were found to be T101+, OKT3+, and Ia-, while E- CFC were OKT3- and Ia+. Using monocyte-depleted populations obtained by sedimentation at unit gravity, lymphocyte colony growth was absent in monocyte-depleted fractions, and optimal growth occurred with 40% monocytes in culture. In contrast to some previous studies, we find that lymphocyte CFC originate from a small, cycling population of cells bearing mature T or B lymphocyte markers. Entry into cell division, however, does not confer colony-forming capacity on lymphocytes. Monocytes are critical to growth of E+ CFC, and cultures severely depleted of monocytes would not be expected to form colonies.

scholarly journals Characterization of normal peripheral blood lymphocyte colony-forming cells: cell cycle status, surface markers, and cellular growth requirements

Blood ◽  
1983 ◽  
Vol 61 (3) ◽  
pp. 548-555 ◽  
Author(s):  
R Taetle ◽  
D To ◽  
A Caviles ◽  
SW Norby ◽  
J Mendelsohn
Keyword(s):  
Cell Cycle ◽  
Peripheral Blood ◽  
B Lymphocyte ◽  
Mononuclear Cells ◽  
Optimal Growth ◽  
Colony Growth ◽  
Cellular Growth ◽  
Peripheral Blood Mononuclear ◽  
Normal Peripheral Blood ◽  
Cell Cycle Status

Abstract We performed a series of studies to further clarify the nature of lymphocyte colony-forming cells (CFC) from normal peripheral blood. Mononuclear cells were separated into E-rosette-enriched (E+) and E- rosette-depleted (E-) populations and cultured in methylcellulose with conditioned media and irradiated mononuclear cells. Linear plating relationships were obtained with plating efficiencies of 0.26% +/- .02% (mean +/- SE) for E+ CFC and 0.18% +/- .02% for E- CFC. Cells in E+ colonies were T lymphocytes and in E- colonies were B lymphocytes as determined by cell surface marker analysis. Using the thymidine suicide technique, approximately one-half of CFC were found to be in cycle at any moment, and plating efficiencies and cell cycle status of E+ CFC were not changed by preincubation with PHA in liquid culture for 48 hr. Using antibody complement-mediated cytotoxicity, E+ CFC were found to be T101+, OKT3+, and Ia-, while E- CFC were OKT3- and Ia+. Using monocyte-depleted populations obtained by sedimentation at unit gravity, lymphocyte colony growth was absent in monocyte-depleted fractions, and optimal growth occurred with 40% monocytes in culture. In contrast to some previous studies, we find that lymphocyte CFC originate from a small, cycling population of cells bearing mature T or B lymphocyte markers. Entry into cell division, however, does not confer colony-forming capacity on lymphocytes. Monocytes are critical to growth of E+ CFC, and cultures severely depleted of monocytes would not be expected to form colonies.

scholarly journals Ionizing radiation regulates long non-coding RNAs in human peripheral blood mononuclear cells

2016 ◽  
Vol 58 (2) ◽  
pp. 201-209 ◽  
Author(s):  
Lucian Beer ◽  
Lucas Nemec ◽  
Tanja Wagner ◽  
Robin Ristl ◽  
Lukas M. Altenburger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Ionizing Radiation ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Non Coding Rnas

AbstractLong non-coding RNAs (lncRNAs) are non-protein coding transcripts that modulate mRNA and microRNA (miRNA) expression, thereby controlling multiple cellular processes, including transcriptional regulation of gene expression, cell differentiation and apoptosis. Ionizing radiation (IR), a strong cellular stressor, is known to influence gene expression of irradiated cells, mainly by activation of oxidative processes. Whether and how IR also affects lncRNA expression in human peripheral blood mononuclear cells (PBMCs) is still poorly understood. Exposure of PBMCs to IR dose-dependently activated p53 and its downstream target p21, ultimately leading to cell-cycle arrest and/or apoptosis. Cleavage of caspase-3, a specific process during apoptotic cell death, was detectable at doses as low as 30 Gy. Transcriptome analysis of 60 Gy–irradiated PBMCs revealed a strong time-dependent regulation of a variety of lncRNAs. Among many unknown lncRNAs we also identified a significant upregulation of Trp53cor1, MEG3 and TUG1, which have been shown to be involved in the regulation of cell cycle and apoptotic processes mediated by p53. In addition, we found 177 miRNAs regulated in the same samples, including several miRNAs that are known targets of upregulated lncRNAs. Our data show that IR dose-dependently regulates the expression of a wide spectrum of lncRNAs in PBMCs, suggesting a crucial role for lncRNAs in the complex regulatory machinery activated in response to IR.

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