LEF-1 is a prosurvival factor in chronic lymphocytic leukemia and is expressed in the preleukemic state of monoclonal B-cell lymphocytosis by Albert Gutierrez,

Slides:

Advertisements

Similar presentations

Glioma-derived soluble factor(s) enhance IL-10 signaling.

Advertisements

Characterization of a rare IL-10–competent B-cell subset in humans that parallels mouse regulatory B10 cells by Yohei Iwata, Takashi Matsushita, Mayuka.

IFNα-stimulated neutrophils and monocytes release a soluble form of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2 ligand) displaying apoptotic activity.

IFN-γ and STAT1 are required for efficient induction of CXC chemokine receptor 3 (CXCR3) on CD4+ but not CD8+ T cells by Joseph Barbi, Steve Oghumu, Claudio.

Lymphoid precursors are directed to produce dendritic cells as a result of TLR9 ligation during herpes infection by Robert S. Welner, Rosana Pelayo, Yoshinori.

CLEC5A is critical for dengue virus–induced inflammasome activation in human macrophages by Ming-Fang Wu, Szu-Ting Chen, An-Hang Yang, Wan-Wan Lin, Yi-Ling.

IL-1β stimulates CXCL5 and CXCL8 gene expression and protein secretion in A549 cells in a time- and dose-dependent manner. IL-1β stimulates CXCL5 and CXCL8.

by Yoko Otake, Sridharan Soundararajan, Tapas K. Sengupta, Ebenezer A

by Susan E. Shetzline, Ravikumar Rallapalli, Kelley J

Aurora-A kinase: a novel target of cellular immunotherapy for leukemia

Transcription factor GATA-1 potently represses the expression of the HIV-1 coreceptor CCR5 in human T cells and dendritic cells by Mark S. Sundrud, Scott.

Further Analysis of Interleukin-2 Receptor Subunit Expression on the Different Human Peripheral Blood Mononuclear Cell Subsets by Denis David, Lynda Bani,

Rapid and selective death of leukemia stem and progenitor cells induced by the compound 4-benzyl, 2-methyl, 1,2,4-thiadiazolidine, 3,5 dione (TDZD-8)‏

TCL1: a shared tumor-associated antigen for immunotherapy against B-cell lymphomas by Jinsheng Weng, Seema Rawal, Fuliang Chu, Hyun Jun Park, Rakesh Sharma,

FOG-1 represses GATA-1-dependent FcϵRI β-chain transcription: transcriptional mechanism of mast-cell-specific gene expression in mice by Keiko Maeda, Chiharu.

Galectin-9 binding to Tim-3 renders activated human CD4+ T cells less susceptible to HIV-1 infection by Shokrollah Elahi, Toshiro Niki, Mitsuomi Hirashima,

Lineages of human T-cell clones, including T helper 17/T helper 1 cells, isolated at different stages of anti–factor VIII immune responses by Ruth A. Ettinger,

Volume 136, Issue 4, Pages e3 (April 2009)

Induction and role of regulatory CD4+CD25+ T cells in tolerance to the transgene product following hepatic in vivo gene transfer by Ou Cao, Eric Dobrzynski,

by Christopher J. Ott, Nadja Kopp, Liat Bird, Ronald M

by Rong Chen, Michael J. Keating, Varsha Gandhi, and William Plunkett

Novel function for interleukin-7 in dendritic cell development

Sustained signaling through the B-cell receptor induces Mcl-1 and promotes survival of chronic lymphocytic leukemia B cells by Aleksandar Petlickovski,

Prostaglandin E2 is a key factor for CCR7 surface expression and migration of monocyte-derived dendritic cells by Elke Scandella, Ying Men, Silke Gillessen,

CD300a is expressed on human B cells, modulates BCR-mediated signaling, and its expression is down-regulated in HIV infection by Rodolfo Silva, Susan Moir,

Increased survival is a selective feature of human circulating antigen-induced plasma cells synthesizing high-affinity antibodies by Inés González-García,

Cytokine-inducible CD40 expression in human endothelial cells is mediated by interferon regulatory factor-1 by Andreas H. Wagner, Matthias Gebauer, Beatrix.

Preactivation with IL-12, IL-15, and IL-18 Induces CD25 and a Functional High-Affinity IL-2 Receptor on Human Cytokine-Induced Memory-like Natural Killer.

Developmental- and differentiation-specific patterns of human γ- and β-globin promoter DNA methylation by Rodwell Mabaera, Christine A. Richardson, Kristin.

Role of IL-9 in the pathophysiology of allergic diseases

Inhibition of glycogen synthase kinase-3 activity leads to epigenetic silencing of nuclear factor κB target genes and induction of apoptosis in chronic.

Surface IgM stimulation induces MEK1/2-dependent MYC expression in chronic lymphocytic leukemia cells by Sergey Krysov, Samantha Dias, Alex Paterson, C.

Chronic neutropenia mediated by Fas ligand

by Andrea Crotti, Marina Lusic, Rossella Lupo, Patricia M. J

Vascular endothelial growth factor stimulates protein kinase CβII expression in chronic lymphocytic leukemia cells by Simon T. Abrams, Benjamin R. B. Brown,

Gene expression and immunologic consequence of SPAN-Xb in myeloma and other hematologic malignancies by Zhiqing Wang, Yana Zhang, Haichao Liu, Emanuela.

The exosome complex establishes a barricade to erythroid maturation

CTLA-4 is not restricted to the lymphoid cell lineage and can function as a target molecule for apoptosis induction of leukemic cells by Maria Pia Pistillo,

The degree of BCR and NFAT activation predicts clinical outcomes in chronic lymphocytic leukemia by Christine Le Roy, Pierre-Antoine Deglesne, Nathalie.

TGF-β combined with M-CSF and IL-4 induces generation of immune inhibitory cord blood dendritic cells capable of enhancing cytokine-induced ex vivo expansion.

Generation of Highly Cytotoxic Natural Killer Cells for Treatment of Acute Myelogenous Leukemia Using a Feeder-Free, Particle-Based Approach Jeremiah.

Cytokine-Release Syndrome in Patients With B-Cell Chronic Lymphocytic Leukemia and High Lymphocyte Counts After Treatment With an Anti-CD20 Monoclonal.

Soluble PD-1 ligands regulate T-cell function in Waldenstrom macroglobulinemia by Shahrzad Jalali, Tammy Price-Troska, Jonas Paludo, Jose Villasboas, Hyo-Jin.

Replacing mouse BAFF with human BAFF does not improve B-cell maturation in hematopoietic humanized mice by Julie Lang, Bicheng Zhang, Margot Kelly, Jacob.

Volume 141, Issue 5, Pages e2 (November 2011)

Dynamic change of transcription pausing through modulating NELF protein stability regulates granulocytic differentiation by Xiuli Liu, Aishwarya A. Gogate,

IL-18, but Not IL-12, Induces Production of IFN-γ in the Immunosuppressive Environment of HPV16 E7 Transgenic Hyperplastic Skin Christina Gosmann, Ian.

Impaired Proteasome Function Activates GATA3 in T Cells and Upregulates CTLA-4: Relevance for Sézary Syndrome Heather M. Gibson, Anjali Mishra, Derek.

T-box 21 transcription factor is responsible for distorted TH2 differentiation in human peripheral CD4+ T cells Osamu Kaminuma, DVM, PhD, Fujiko Kitamura,

by Kamira Maharaj, John J

by Silvia Mele, Stephen Devereux, Andrea G

Response of monocytes to hY4 delivery and cytokine levels in CLL serum

Autocrine IL-21 Stimulation Is Involved in the Maintenance of Constitutive STAT3 Activation in Sézary Syndrome Leslie van der Fits, Jacoba J. Out-Luiting,

Impaired natural killer cell functions in patients with signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations Giovanna.

Volume 24, Issue 9, Pages (September 2016)

Myeloma cell–derived Runx2 promotes myeloma progression in bone

T exosomes bind MAdCAM-1 via RA-increased integrin α4β7.

Defective negative regulation of Toll-like receptor signaling leads to excessive TNF-α in myeloproliferative neoplasm by Hew Yeng Lai, Stefan A. Brooks,

The IL-6 Trans-Signaling-STAT3 Pathway Mediates ECM and Cellular Proliferation in Fibroblasts from Hypertrophic Scar Sutapa Ray, Xiaoxi Ju, Hong Sun,

Increased Expression of Wnt2 and SFRP4 in Tsk Mouse Skin: Role of Wnt Signaling in Altered Dermal Fibrillin Deposition and Systemic Sclerosis Julie Bayle,

Josée Lamoureux, PhD, Jana Stankova, PhD, Marek Rola-Pleszczynski, MD

Volume 32, Issue 6, Pages (June 2010)

Figure 1 CD52 expression on innate myeloid and lymphoid cell subsets

Decreased expression of cell cycle– and apoptosis-related genes in Aml1-excised leukemia cell. Decreased expression of cell cycle– and apoptosis-related.

Senescence-associated defective HLA-DR upregulation does not modulate immunosuppressive properties of MSCs. (A) Fit and senescent MSCs were subjected to.

Interleukin-17A Promotes IgE Production in Human B Cells

Volume 28, Issue 5, Pages (May 2008)

The Akt/Mcl-1 pathway plays a prominent role in mediating antiapoptotic signals downstream of the B-cell receptor in chronic lymphocytic leukemia B cells.

Volume 126, Issue 5, Pages (May 2004)

Secretion of TNF-α from macrophages and monocytic cells were reduced by the deletion of Nrdc. Secretion of TNF-α from macrophages and monocytic cells were.

Presentation transcript:

LEF-1 is a prosurvival factor in chronic lymphocytic leukemia and is expressed in the preleukemic state of monoclonal B-cell lymphocytosis by Albert Gutierrez, Renee C. Tschumper, Xiaosheng Wu, Tait D. Shanafelt, Jeanette Eckel-Passow, Paul M. Huddleston, Susan L. Slager, Neil E. Kay, and Diane F. Jelinek Blood Volume 116(16):2975-2983 October 21, 2010 ©2010 by American Society of Hematology

Deregulation of Wnt pathway gene expression in CLL Deregulation of Wnt pathway gene expression in CLL. (A) Detection of LEF1, WNT3, TCF4 [ITF-2], and CCND2 mRNA levels by quantitative PCR in leukemic or normal B cells from 8 CLL patients and 3 healthy donor samples, respectively. Deregulation of Wnt pathway gene expression in CLL. (A) Detection of LEF1, WNT3, TCF4 [ITF-2], and CCND2 mRNA levels by quantitative PCR in leukemic or normal B cells from 8 CLL patients and 3 healthy donor samples, respectively. Transcript levels were normalized to 18s rRNA, and relative fold change was calculated using the 2−ΔΔCT method. *P < .05. Error bars represent SEM. (B) Detection of IGFBP-4 protein secretion into culture media by ELISA in B cells from 6 CLL patients and 3 healthy donor samples. The dashed line at 5 ng/mL indicates the ELISA threshold level of IGFBP-4 detection, and the horizontal lines indicate the mean of each group. Albert Gutierrez Jr et al. Blood 2010;116:2975-2983 ©2010 by American Society of Hematology

LEF-1 protein is specifically expressed by B-cell precursors and CLL cells but not mature peripheral B-cell subsets. LEF-1 protein is specifically expressed by B-cell precursors and CLL cells but not mature peripheral B-cell subsets. (A) Representative intracellular flow cytometry for LEF-1 in B cells from healthy donor bone marrow, blood, tonsil, cord blood, and CLL B cells from a CLL patient. Isotype control histogram is shaded gray; LEF-1 histogram is black. (B) Detection of LEF1 and AICDA mRNA levels by quantitative PCR in B cells from a healthy donor at 24 and 72 hours after stimulation with CpG and cytokines or anti-immunoglobulin (anti-Ig) stimulation. Fold change was calculated relative to unstimulated donor B cells; an unstimulated CLL sample served as a positive control for LEF-1 expression. (C) Detection of LEF1 mRNA levels by quantitative PCR in 2 CLL patients before and after 2 weeks in culture in AIM-V media at a density of 10 × 106 cells/mL. (D) Western blot analysis of LEF-1 isoforms in B cells from 7 CLL samples; T cells from a healthy donor and Colo 320 cells served as a control for LEF-1 isoforms. β-Actin shown as a loading control of samples. Albert Gutierrez Jr et al. Blood 2010;116:2975-2983 ©2010 by American Society of Hematology

Activation of the Wnt pathway in CLL cells and not in normal mature B cells. Activation of the Wnt pathway in CLL cells and not in normal mature B cells. (A) TCF/LEF dual luciferase reporter assay relative fold change of positive reporter samples from 6 unmutated CLL samples, 10 mutated CLL samples, and 3 normal B-cell samples. *P = .024. **P = .014. Horizontal lines indicate the mean of the group. (B) Western blot analysis of β-catenin in 6 CLL and 2 normal B-cell samples. β-Actin shown as a loading control of samples. Albert Gutierrez Jr et al. Blood 2010;116:2975-2983 ©2010 by American Society of Hematology

LEF-1 is a prosurvival factor in CLL cells. LEF-1 is a prosurvival factor in CLL cells. (A) Detection of LEF1 mRNA levels by quantitative PCR in B cells from a CLL patient 24 hours after siRNA treatment. (B) Intracellular flow cytometry measurements of LEF-1 expression with indicated change in mean fluorescence intensity (ΔMFI) 72 hours after siRNA treatment in 9 CLL samples. *P < .0001. **P < .0001. Horizontal lines indicate the mean of the group. (C) CLL percentage survival 72 hours after siRNA treatment in 9 samples (left panel), and the average fold change in survival normalized to control siRNA treatment (right panel). *P = .0001. **P = .0002. Error bars represent the SEM. Albert Gutierrez Jr et al. Blood 2010;116:2975-2983 ©2010 by American Society of Hematology

CD19+/CD5+ cells of the CLL precursor state MBL express LEF-1. CD19+/CD5+ cells of the CLL precursor state MBL express LEF-1. (A) Three representative flow cytometric analyses of peripheral blood mononuclear cells from MBL patients stained with anti-CD19, CD5, and LEF-1 antibodies. Isotype control histogram is shaded gray; LEF-1 histogram is black. Data are representative of results obtained with 8 MBL patients. (B) The change in mean fluorescence intensity (ΔMFI) between isotype and anti–LEF-1 staining in 8 MBL and 13 CLL samples. *P = .002. Horizontal lines indicate the mean of the group. Albert Gutierrez Jr et al. Blood 2010;116:2975-2983 ©2010 by American Society of Hematology