Human chronic lymphocytic leukemia B cells can escape DNA damage-induced apoptosis through the nonhomologous end-joining DNA repair pathway by Ludovic.

Slides:

Advertisements

Similar presentations

Volume 114, Issue 5, Pages (May 1998)

Advertisements

In Cardiomyocyte Hypoxia, Insulin-Like Growth Factor-I-Induced Antiapoptotic Signaling Requires Phosphatidylinositol-3-OH-Kinase-Dependent and Mitogen-Activated.

Circulating IL-15 exists as heterodimeric complex with soluble IL-15Rα in human and mouse serum by Cristina Bergamaschi, Jenifer Bear, Margherita Rosati,

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

A novel SHP-1/Grb2–dependent mechanism of negative regulation of cytokine-receptor signaling: contribution of SHP-1 C-terminal tyrosines in cytokine signaling.

Implications of somatic mutations in the AML1 gene in radiation-associated and therapy-related myelodysplastic syndrome/acute myeloid leukemia by Hironori.

Comparison of Caspase Activation and Subcellular Localization in HL-60 and K562 Cells Undergoing Etoposide-Induced Apoptosis by Luis M. Martins, Peter.

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

by Madhu Gupta, Paul T. Mungai, and Eugene Goldwasser

by Hong Hao, Huiling Qi, and Manohar Ratnam

by Ji-Long Chen, Andre Limnander, and Paul B. Rothman

Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor–κB and IκBα kinase in human multiple myeloma cells, leading to.

The TCL1 oncoprotein inhibits activation-induced cell death by impairing PKCθ and ERK pathways by Gilles Despouy, Marjorie Joiner, Emilie Le Toriellec,

by Paritosh Ghosh, Meredith A

Rituximab-induced tumor cell agglutination

Constitutively activated phosphatidylinositol-3 kinase (PI-3K) is involved in the defect of apoptosis in B-CLL: association with protein kinase Cδ by Ingo.

by Kumudha Balakrishnan, William G. Wierda, Michael J

Overexpression of survivin in primary ATL cells and sodium arsenite induces apoptosis by down-regulating survivin expression in ATL cell lines by Xiao-Fang.

Downstream effectors of oncogenic ras in multiple myeloma cells

Caspases Mediate Tumor Necrosis Factor-–Induced Neutrophil Apoptosis and Downregulation of Reactive Oxygen Production by Kouhei Yamashita, Atsushi Takahashi,

Constitutive Phosphorylation of Focal Adhesion Kinase Is Involved in the Myofibroblast Differentiation of Scleroderma Fibroblasts Yoshihiro Mimura, Hironobu.

ARG tyrosine kinase activity is inhibited by STI571

Keloid Fibroblasts Resist Ceramide-Induced Apoptosis by Overexpression of Insulin- Like Growth Factor I Receptor Hiroshi Ishihara, Hiroshi Yoshimoto,

Albumin activates the AKT signaling pathway and protects B-chronic lymphocytic leukemia cells from chlorambucil- and radiation-induced apoptosis by Dylan.

Nanomolar concentration of NSC606985, a camptothecin analog, induces leukemic-cell apoptosis through protein kinase Cδ–dependent mechanisms by Man-Gen.

by Susana Constantino Rosa Santos, and Sérgio Dias

Effects of Betulinic Acid Alone and in Combination with Irradiation in Human Melanoma Cells Edgar Selzer, Emilio Pimentel, Volker Wacheck, Werner Schlegel,

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

Chronic neutropenia mediated by Fas ligand

Oxidative Damage to RPA Limits the Nucleotide Excision Repair Capacity of Human Cells Melisa Guven, Reto Brem, Peter Macpherson, Matthew Peacock, Peter.

by Beatriz Bellosillo, Mireia Dalmau, Dolors Colomer, and Joan Gil

Volume 6, Issue 2, Pages (February 1997)

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

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,

Constitutive STAT6 activation in primary mediastinal large B-cell lymphoma by Chrystelle Guiter, Isabelle Dusanter-Fourt, Christiane Copie-Bergman, Marie-Laure.

by Xingwei Sui, Sanford B. Krantz, Min You, and Zhizhuang Zhao

Regulation of Akt-dependent cell survival by Syk and Rac

Volume 122, Issue 5, Pages (May 2002)

Stimulation of the B-cell receptor activates the JAK2/STAT3 signaling pathway in chronic lymphocytic leukemia cells by Uri Rozovski, Ji Yuan Wu, David.

TRAIL-induced apoptosis of authentic myeloma cells does not correlate with the procaspase-8/cFLIP ratio by Andrew Spencer, Sung-Lin Yeh, Karly Koutrevelis,

Bone morphogenetic protein-2 induces apoptosis in human myeloma cells with modulation of STAT3 by Chiharu Kawamura, Masahiro Kizaki, Kenji Yamato, Hideo.

A DNA Damage Response Pathway Controlled by Tel1 and the Mre11 Complex

Volume 119, Issue 3, Pages (September 2000)

Differential Modulation of Ku70/80 DNA-Binding Activity in a Patient with Multiple Basal Cell Carcinomas Paola Mazzarelli, Carla Rabitti, Paola Parrella,

Volume 120, Issue 5, Pages (April 2001)

Volume 130, Issue 4, Pages (August 2007)

Volume 44, Issue 5, Pages (December 2011)

PDGF regulates gap junction communication and connexin43 phosphorylation by PI 3- kinase in mesangial cells Jian Yao, Tetsuo Morioka, Takashi Oite Kidney.

Volume 63, Issue 2, Pages (February 2003)

Volume 17, Issue 6, Pages (December 1996)

PARP1 Represses PAP and Inhibits Polyadenylation during Heat Shock

Northern blot and Western blot analysis of syndecan-4 expression in TF-1 and HEL cells. Northern blot and Western blot analysis of syndecan-4 expression.

Volume 93, Issue 5, Pages (May 1998)

Anne T. Funding, Claus Johansen, Matthias Gaestel, Bo M

Volume 118, Issue 1, Pages (July 2004)

Volume 66, Issue 4, Pages e5 (May 2017)

PARP Determines the Mode of Cell Death in Skin Fibroblasts, but not Keratinocytes, Exposed to Sulfur Mustard Dana Anderson, Betty Benton, Zhao-Qi Wang,

Characterization of Keratinocyte Differentiation Induced by Ascorbic Acid: Protein Kinase C Involvement and Vitamin C Homeostasis1 Isabella Savini, Antonello.

Gang Li, Jason A. Bush, Vincent C. Ho

Volume 39, Issue 1, Pages (July 2010)

Volume 119, Issue 5, Pages (November 2000)

1α,25-Dihydroxyvitamin D3 Stimulates Activator Protein 1 DNA-Binding Activity by a Phosphatidylinositol 3-Kinase/Ras/MEK/Extracellular Signal Regulated.

Volume 58, Issue 1, Pages (July 2000)

Effects of SYCE2 expression on DSB repair.

CML-HSA treatment activates MAPK family members ERK1/2 and p38 but not JNK. Samples were taken at the indicated times after 100 μg/ml CML-HSA exposure.

Bcl-2 and bcl-xL Antisense Oligonucleotides Induce Apoptosis in Melanoma Cells of Different Clinical Stages Robert A. Olie, Christoph Hafner, Renzo Küttel,

IAA inhibits PI3K, MKK4, and MKK7 kinase activities by directly binding in an ATP-competitive manner. IAA inhibits PI3K, MKK4, and MKK7 kinase activities.

Suppression of Keratinocyte Growth and Differentiation by Transforming Growth Factor β1 Involves Multiple Signaling Pathways Alison L. Dahler, Lois L.

Volume 13, Issue 1, Pages (October 2015)

Interaction of NHEJ and HR pathways in PCO cultures.

Presentation transcript:

Human chronic lymphocytic leukemia B cells can escape DNA damage-induced apoptosis through the nonhomologous end-joining DNA repair pathway by Ludovic Deriano, Olivier Guipaud, Hélène Merle-Béral, Jacques-Louis Binet, Michelle Ricoul, Gaby Potocki-Veronese, Vincent Favaudon, Zofia Maciorowski, Catherine Muller, Bernard Salles, Laure Sabatier, and Jozo Delic Blood Volume 105(12):4776-4783 June 15, 2005 ©2005 by American Society of Hematology

B-CLL cell sensitivity to DSB-induced apoptosis. B-CLL cell sensitivity to DSB-induced apoptosis. R indicates resistant B-CLL cells; and S, sensitive B-CLL cells. (A) Sensitivity of B-CLL cells to γ-irradiation-induced apoptosis (R: n = 13 samples; S: n = 79 samples). Sensitivity of R (n = 5 samples) and S (n = 15 samples) B-CLL cells to NCS-induced (B), VP16-induced (C), and okadaic acid-induced (D) apoptosis. Percentages of apoptotic cells are the means (± SEM) of duplicate experiments on B-CLL samples. Ludovic Deriano et al. Blood 2005;105:4776-4783 ©2005 by American Society of Hematology

The PI-3 kinase inhibitor wortmannin and the DNA-PKcs inhibitor NU7026 sensitize resistant B-CLL cells to γ-irradiation-induced apoptosis. The PI-3 kinase inhibitor wortmannin and the DNA-PKcs inhibitor NU7026 sensitize resistant B-CLL cells to γ-irradiation-induced apoptosis. R indicates resistant B-CLL (n = 5 samples); and S, sensitive B-CLL (n = 7 samples). (A) B-CLL cells were either left untreated (NT) or treated with 1 μM wortmannin alone (WM), with 10 Gy irradiation alone (IR) or with 1 μM wortmannin and 10 Gy irradiation (IR+WM). (B) B-CLL cells were either left untreated (NT) or treated with 10 μM NU7026 alone (NU7026), with 10 Gy irradiation alone (IR), or with 10 μM NU7026 and 10 Gy irradiation (IR+NU7026). Percentages of apoptotic cells are means (± SEM) of duplicate experiments on n B-CLL samples. Ludovic Deriano et al. Blood 2005;105:4776-4783 ©2005 by American Society of Hematology

NHEJ DNA repair pathway is overactivated in resistant B-CLL cells after DNA damage. NHEJ DNA repair pathway is overactivated in resistant B-CLL cells after DNA damage. (A) NHEJ activity in untreated cells (Irradiation -) and cells exposed to 10 Gy irradiation (Irradiation +). Assays were carried out using a resistant B-CLL lymphocyte extract (R), a sensitive B-CLL cell extract (S), and an EBV-transformed B-lymphocyte extract (B cells). The results shown are representative of those obtained with all the cell extracts tested (n = 3 for resistant B-CLL samples, n = 3 for sensitive B-CLL samples, and n = 3 for EBV-transformed B-cell samples). (B) Changes in NHEJ activity after exposure to 10 Gy irradiation were calculated from the mean (± SEM) activities recorded in duplicate experiments on 3 different resistant B-CLL cell extracts (R), 3 different sensitive B-CLL cell extracts (S), and 3 different EBV-transformed B-lymphocyte extracts (B cells). (C) NHEJ activity in cells that were either left untreated (-) or treated (+) with 10 Gy irradiation, 1 μM wortmannin, or 10 μM NU7026. Assays were performed on resistant B-CLL cell extracts (R) and sensitive B-CLL cell extracts (S). A representative experiment is shown. (D) NHEJ activity assay with DNA-PKcs-deficient cell line extract (MO59J) and wild-type cell line extract (MO59K). A representative experiment is shown. See Supplemental Figure S1 for more information. Ludovic Deriano et al. Blood 2005;105:4776-4783 ©2005 by American Society of Hematology

Early increases in DNA-PKcs activity in resistant B-CLL cell extracts after γ-irradiation. Early increases in DNA-PKcs activity in resistant B-CLL cell extracts after γ-irradiation. (A) DNA-PKcs activity in resistant B-CLL (R) nuclear protein extracts (25 μg/lane) and sensitive B-CLL (S) nuclear protein extracts (25 μg/lane) at the indicated times after treatment with 10 Gy γ-irradiation. The results shown are representative of those obtained in all extracts tested (n = 3 for resistant samples and n = 3 for sensitive samples). (B) DNA-PKcs activity in untreated nuclear protein extracts from 3 resistant B-CLL samples (R1,R2,R3) and from 3 sensitive B-CLL samples (S1,S2,S3). (C) Mean (± SEM) DNA-PKcs activity in 3 resistant B-CLL samples (R) and 3 sensitive B-CLL samples (S) at the indicated times after irradiation. Values are given in arbitrary units (AU). (D) DNA-PKcs activity in resistant (R) and sensitive (S) B-CLL nuclear protein extracts (25 μg/lane) from cells that were either left untreated (-) or treated with 10 Gy irradiation (+, measurements were carried out 15 minutes after irradiation), 1 μM wortmannin, or 10 μM NU7026. A representative experiment is shown. See Supplemental Figure S2 for more information. Ludovic Deriano et al. Blood 2005;105:4776-4783 ©2005 by American Society of Hematology

Constitutive increase in Ku70/80 heterodimer DNA-end binding activity. Constitutive increase in Ku70/80 heterodimer DNA-end binding activity. (A) Ku DNA-end binding activity in whole protein extracts from resistant (R) and sensitive B-CLL (S) cells (1 μg/lane) at the indicated times after treatment with 10 Gy γ-irradiation. The results shown are representative of those obtained in all extracts tested (n = 3 for resistant samples and n = 3 for sensitive samples). (B) Ku DNA-end binding activity (mean ± SEM in arbitrary units, AU) in 3 resistant B-CLL samples (R) and 3 sensitive B-CLL samples (S) at the indicated times after irradiation. (C) Untreated whole cell protein extracts (1 μg/lane) from the Ku80-deficient xrs6 cell line and the CHO-K1 line (expressing both Ku70 and Ku80 proteins). MO59J (DNA-PKcs deficient) and MO59K (normal levels of DNA-PKcs activity) were used as controls. (D) Untreated B-CLL lymphocyte protein extracts (5 μg, lane 1) were immunodepleted using 125 ng (lane 2) and 250 ng (lane 3) monoclonal Ku70 antibody, assayed for Ku DNA-end binding activity (1 μg protein extract/lane) (upper panel) and then subjected to Western blot (WB) analysis (lower panel). For supershift assays (lanes 4-5), samples were treated with 5 μg untreated B-CLL lymphocyte protein extract (lane 5) or with 250 ng polyclonal Ku70 antibody (lane 4), and then assayed for Ku DNA-end binding (1 μg of protein extract/lane). (E) Whole-cell extracts (5 μg) were obtained from representative sensitive and resistant B-CLL cell samples at the indicated times after irradiation. Extracts were subjected to electrophoresis on a 10% SDS polyacrylamide gel (DNA-PKcs analysis was carried out using a 6% SDS polyacrylamide gel). Proteins were then blotted onto polyvinylidenefluoride (PVDF) membranes and were detected using the appropriate antibodies. (F) Whole-cell extracts (5 μg) from 6 sensitive (S) and 4 resistant (R) untreated B-CLL cell samples, and 4 untreated normal B-cell samples from healthy donors (B cells) were subjected to Western blotting analysis as described in panel E. See Supplemental Figure S3 for more information. Ludovic Deriano et al. Blood 2005;105:4776-4783 ©2005 by American Society of Hematology