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Cancer: Chronic Lymphocytic Leukemia

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Total 43 results found since Jan 2013.

Paclitaxel induces apoptosis in leukemia cells through a JNK activation-dependent pathway.
Abstract Paclitaxel (PTX) is a mitotic inhibitor widely used in chemotherapy for many types of cancers, including solid tumors and hematological malignancies. However, the molecular basis of the anti-proliferation activity of PTX is not fully understood. In this paper, we focused on the role of c-Jun N-terminal kinase (JNK) pathways in PTX-induced apoptosis and proliferation inhibition. The effects of PTX were examined in human leukemia cell lines and patients' chronic lymphocytic leukemia (CLL) cells in relation to mitochondrial events, apoptosis, and perturbation of JNK activation using flow cytometry, siRNA, mi...
Source: Genetics and Molecular Research - March 19, 2016 Category: Genetics & Stem Cells Authors: Peng ZG, Liu DC, Yao YB, Feng XL, Huang X, Tang YL, Yang J, Wang XX Tags: Genet Mol Res Source Type: research

Wnt5a induces ROR1/ROR2 heterooligomerization to enhance leukemia chemotaxis and proliferation
This study identifies an interaction between ROR1 and ROR2 that is required for Wnt5a signaling that promotes leukemia chemotaxis and proliferation.
Source: Journal of Clinical Investigation - December 22, 2015 Category: Biomedical Science Authors: Jian Yu, Liguang Chen, Bing Cui, George F. Widhopf II, Zhouxin Shen, Rongrong Wu, Ling Zhang, Suping Zhang, Steven P. Briggs, Thomas J. Kipps Source Type: research

Abstract 3974: A preclinical study for miR181b as therapeutic in Eu-TCL1FL-tg mouse model for CLL
Chronic lymphocytic leukemia (CLL) is a malignancy of B cells with immunophenotype of memory cells. Downstream pathways to BCR, like NFkB, AKT and ERK, and anti-apoptotic proteins such as Bcl2 and Mcl1, are thought to contribute to expansion and survival of the malignant cells. CLL patients show different clinical course: tumor clones having no V-gene mutations, many CD38+ or ZAP-70+ B cells, chromosome 11q deletion and high expression of TCL1, had an aggressive, usually fatal course, whereas patients with mutated clones, few CD38+ or ZAP-70+ B cells and low TCL1 expression, had an indolent course. Recent studies identifie...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Bresin, A., Callegari, E., D'Abundo, L., Cattani, C., Bassi, C., Zagatti, B., Narducci, M. G., Caprini, E., Pekarsky, Y., Croce, C. M., Sabbioni, S., Negrini, M., Russo, G. Tags: Molecular and Cellular Biology Source Type: research

miR-181b as a therapeutic agent for chronic lymphocytic leukemia in the Eµ-TCL1 mouse model.
Authors: Bresin A, Callegari E, D'Abundo L, Cattani C, Bassi C, Zagatti B, Narducci MG, Caprini E, Pekarsky Y, Croce CM, Sabbioni S, Russo G, Negrini M Abstract The involvement of microRNAs (miRNAs) in chronic lymphocytic leukemia (CLL) pathogenesis suggests the possibility of anti-CLL therapeutic approaches based on miRNAs. Here, we used the Eµ-TCL1 transgenic mouse model, which reproduces leukemia with a similar course and distinct immunophenotype as human B-CLL, to test miR-181b as a therapeutic agent.In vitro enforced expression of miR-181b mimics induced significant apoptotic effects in human B-cell lines (RA...
Source: Oncotarget - June 22, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Regulation of p53 and Rb Links the Alternative NF-κB Pathway to EZH2 Expression and Cell Senescence
by Alessio Iannetti, Adeline C. Ledoux, Susan J. Tudhope, Hélène Sellier, Bo Zhao, Sophia Mowla, Adam Moore, Holger Hummerich, Benjamin E. Gewurz, Simon J. Cockell, Parmjit S. Jat, Elaine Willmore, Neil D. Perkins There are two major pathways leading to induction of NF-κB subunits. The classical (or canonical) pathway typically leads to the induction of RelA or c-Rel containing complexes, and involves the degradation of IκBα in a manner dependent on IκB kinase (IKK) β and the IKK regulatory subunit NEMO. The alternative (or non-canonical) pathway, involves the inducible processing of p100 to p52, leading to the ind...
Source: PLoS Genetics - September 25, 2014 Category: Genetics & Stem Cells Authors: Alessio Iannetti et al. Source Type: research

STAT3 Activates GM-CSFR{alpha} in CLL
Here, it was determined that chronic lymphocytic leukemia (CLL) cells express the α subunit, but not the β subunit, of the granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR/CSF2R). GM-CSFRα was detected on the surface, in the cytosol, and in the nucleus of CLL cells via confocal microscopy, cell fractionation, and GM-CSFRα antibody epitope mapping. Because STAT3 is frequently activated in CLL and the GM-CSFRα promoter harbors putative STAT3 consensus binding sites, MM1 cells were transfected with truncated forms of the GM-CSFRα promoter, then stimulated with IL6 to activa...
Source: Molecular Cancer Research - September 11, 2014 Category: Cancer & Oncology Authors: Li, P., Harris, D., Liu, Z., Rozovski, U., Ferrajoli, A., Wang, Y., Bueso-Ramos, C., Hazan-Halevy, I., Grgurevic, S., Wierda, W., Burger, J., O'Brien, S., Faderl, S., Keating, M., Estrov, Z. Tags: Genomics Source Type: research

Gene expression profile analysis of SUDHL6 cells with siRNA-mediated BCL11 A downregulation.
Abstract Our previous study has shown that downregulation of B-cell chronic lymphocytic leukemia (CLL)/lymphoma11A (BCL11A) gene by small interfering RNA (siRNA) results in the growth inhibition and apoptosis of B cell lymphoma cell line SUDHL6. To gain further insight into the molecular mechanisms of this process and identify the differentially expressed genes in SUDHL6 cells after BCL11A downregulation, the global gene expression profile was identified and analyzed using the Affymetrix HG-U133 Plus 2.0 array.Twenty-one differentially expressed genes were validated and analyzed from the BCL11 A siRNA-treated SUDH...
Source: Cell Biology International - July 7, 2014 Category: Cytology Authors: Wu H, Li Y Tags: Cell Biol Int Source Type: research

Combination of BCL11A siRNA with vincristine increases the apoptosis of SUDHL6 cells
Conclusions The combination of BCL11A siRNA and VCR increases apoptosis in SUDHL6 cells. Our study implies that BCL11A siRNA in combination with VCR may be a useful approach for improving effective treatment for B cell lymphoma.
Source: European Journal of Medical Research - June 24, 2014 Category: Research Source Type: research

Tiam1/Rac1 signals contribute to the proliferation and chemoresistance, but not motility, of chronic lymphocytic leukemia cells
Signals from the tumor microenvironment promote the migration, survival, and proliferation of chronic lymphocytic leukemia (CLL) cells. Rho GTPases control various signaling pathways downstream of microenvironmental cues. Here, we analyze the function of Rac1 in the motility and proliferation of CLL cells. We found decreased transcription of the Rac guanine nucleotide exchange factors Tiam1 and Vav1 in unstimulated peripheral blood CLL cells with almost complete loss of Tiam1 but increased transcription of the potential Rac antagonist RhoH. Consistently, stimulation of CLL cells with the chemokine CXCL12 induced RhoA but n...
Source: Blood - April 3, 2014 Category: Hematology Authors: Hofbauer, S. W., Krenn, P. W., Ganghammer, S., Asslaber, D., Pichler, U., Oberascher, K., Henschler, R., Wallner, M., Kerschbaum, H., Greil, R., Hartmann, T. N. Tags: Lymphoid Neoplasia Source Type: research

The Nedd8-Activating Enzyme Inhibitor MLN4924 Thwarts Microenvironment-Driven NF-κB Activation and Induces Apoptosis in Chronic Lymphocytic Leukemia B Cells.
CONCLUSIONS: MLN4924 disrupts NF-κB activation and induces Bim expression in CLL cells, thereby preventing stroma-mediated resistance. Our data provide rationale for further evaluation of MLN4924 in CLL. Clin Cancer Res; 20(6); 1576-89. ©2014 AACR. PMID: 24634471 [PubMed - in process]
Source: Clinical Cancer Research - March 15, 2014 Category: Cancer & Oncology Authors: Godbersen JC, Humphries LA, Danilova OV, Kebbekus PE, Brown JR, Eastman A, Danilov AV Tags: Clin Cancer Res Source Type: research

Arsenic trioxide induces apoptosis in B-cell chronic lymphocytic leukemic cells through down-regulation of survivin via the p53-dependent signaling pathway
Abstract: Arsenic trioxide (As2O3) can induce apoptosis in many tumors. However, the associated mechanisms are not clearly understood. We found that As2O3 significantly inhibited the proliferation of WSU-CLL cells and induced apoptosis in dose- and time-dependent manners. WSU-CLL cells treated with 2μM As2O3 showed survivin down-regulation and p53 up-regulation. Survivin siRNA combined with As2O3 further inhibited the proliferation of WSU-CLL cells. p53 inhibition by siRNA prevented the down-regulation of survivin by As2O3 and prevented the As2O3-induced cytotoxicity of WSU-CLL cells. These results suggest that As2O3 may ...
Source: Leukemia Research - November 11, 2013 Category: Hematology Authors: Xiao-Hui Zhang, Ru Feng, Meng Lv, Qian Jiang, Hong-Hu Zhu, Ya-Zhen Qing, Jia-Ling Bao, Xiao-Jun Huang, X. Long Zheng Tags: Laboratory Studies Source Type: research

Increasing the complexity of chromatin: functionally distinct roles for replication-dependent histone H2A isoforms in cell proliferation and carcinogenesis
Replication-dependent histones are encoded by multigene families found in several large clusters in the human genome and are thought to be functionally redundant. However, the abundance of specific replication-dependent isoforms of histone H2A is altered in patients with chronic lymphocytic leukemia. Similar changes in the abundance of H2A isoforms are also associated with the proliferation and tumorigenicity of bladder cancer cells. To determine whether these H2A isoforms can perform distinct functions, expression of several H2A isoforms was reduced by siRNA knockdown. Reduced expression of the HIST1H2AC locus leads to in...
Source: Nucleic Acids Research - October 31, 2013 Category: Research Authors: Singh, R., Mortazavi, A., Telu, K. H., Nagarajan, P., Lucas, D. M., Thomas-Ahner, J. M., Clinton, S. K., Byrd, J. C., Freitas, M. A., Parthun, M. R. Tags: Gene Regulation, Chromatin and Epigenetics Source Type: research

Autophagy and ER stress play an essential role in the mechanism of action and drug resistance of the cyclin-dependent kinase inhibitor flavopiridol.
Abstract Chronic lymphocytic leukemia (CLL) is a mature B cell malignancy and is the most prevalent type of leukemia in adults. There is no curative therapy for this disease; however, several new agents have shown very promising results. Autophagy has not been studied in CLL and in this study we first sought to determine if autophagy was functional in CLL with classic inducers, and if this contributes to direct cytotoxicity or protection from cell death. While autophagy is activated with all classic stimuli of this process, only unfolded protein endoplasmic reticulum (ER) stress-mediated autophagy protects from ce...
Source: Autophagy - February 26, 2013 Category: Cytology Authors: Mahoney E, Byrd JC, Johnson AJ Tags: Autophagy Source Type: research