Caspase-mediated Cell Death in Hematological Malignancies: Theoretical Considerations, Methods of Assessment, and Clinical Implications

References

• Kitada, S., Pedersen, I.M., Schinuner, A.D. and Reed, J.C. (2002) "Dysregulation of apoptosis genes in hematopoietic malignan-cies", Oncogene 21, 3459–3474.
   PubMed Web of Science ®Google Scholar
• Blagosklonny, M.V. (2000) "The dilemma of apoptosis in myelodysplasia and leukemia: a new promise of therapeutic intervention?", Leukemia 14, 2017–2018.
   PubMed Web of Science ®Google Scholar
• Susin, S.A., Lorenzo, H.K., Zamzami, N., Marzo, I., Snow, BE., Brothers, G.M., Mangion, J., Jacotot, E., Costantini, P., Loeffler, M., Larochette, N., Goodlett, DR., Aebersold, R., Siderovski, D.P., Penninger, J.M. and Kroemer, G. (1999) "Molecular characterization of mitochondrial apoptosis-inducing factor", Nature 97, 441–446.
   Google Scholar
• Penninger, J.M. (2001) "Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death", Nature 410, 549–554.
   PubMed Web of Science ®Google Scholar
• Perez-Galan, P., Marzo, I., Giraldo, P., Rubio-Felix, D., Lasierra, P., Larrad, L., Anel, A. and Naval, J. (2002) "Role of caspases and apoptosis-inducing factor (AIF) in cladribine-induced apoptosis of B cell chronic lymphocytic leukemia", Leukemia 16, 2106–2114.
   PubMed Web of Science ®Google Scholar
• Earnshaw, W.C., Martins, L.M. and Kaufmann, S.H. (1999) "Mammalian caspases: structure, activation, substrates, and functions during apoptosis", Annu. Rev. Biochem. 68, 383–424.
   PubMed Web of Science ®Google Scholar
• Eked, P.G., Silke, J. and Vaux, D.L. (1999) "Caspase inhibitors", Cell Death Differ 6, 1081–1086.
   PubMed Web of Science ®Google Scholar
• Nicholson, D.W. (1999) "Caspase structure, proteolytic substrates and function during apoptotic cell death", Cell Death Differ 6, 1028–1042.
   PubMed Web of Science ®Google Scholar
• Stennicke, H.R. and Salvesen, G.S. (1999) "Catalytic properties of the caspases", Cell Death Differ 6, 1054–1059.
   PubMed Web of Science ®Google Scholar
• Stennicke, H.R. and Salvesen, G.S. (2000) "Caspases—controlling intracellular signals by protease zymogen activation", Biochem. Biophys. Acta 1477, 299–306.
   PubMed Web of Science ®Google Scholar
• Chinnaiyan, A.M., O'Rourke, K., Yu, G.L., Lyons, R.H., Garg, M., Duan, DR., Xing, L., Gentz, R., Ni, J. and Dixit, V.M. (1996) "Signal transduction by DR3, a death domain-containing receptor related to TNFR-1 and CD95", Science 274, 990–992.
   Google Scholar
• Itoh, N. and Nagata, S. (1993) "A novel protein domain required for apoptosis. Mutational analysis of human Fos antigen", J. Biol. Chem. 268, 10932–10937.
   PubMed Web of Science ®Google Scholar
• Gong, B. and Almasan, A. (2000) "Apo2 ligand/TNF-related apoptosis-inducing ligand and death receptor 5 mediate the apoptotic signaling induced by ionizing radiation in leukemic cells", Cancer Res. 60, 5754–5760.
   PubMed Web of Science ®Google Scholar
• Pan, G., O'Rourke, K., Chinnayan, A.M., Gentz, R., Ebner, R., Ni, J. and Dixit, V.M. (1997) "The receptor for the cytotoxic ligand TRAIL", Science 276, 111–113.
   Google Scholar
• Kim, Y, Suh, N., Sporn, M. and Reed, J.C. (2002) "An inducible pathways for degradation of FLIP protein sensitises tumor cells to TRAIL-induced apoptosis", J. Biol. Chem. 277, 22320–22329.
   PubMed Web of Science ®Google Scholar
• Thornbeny, N.A., Rano, TA., Peterson, E.P., Rasper, D.M., Timkey, T., Garcia-Calvo, M., Houtzager, V.M., Nordstrom, PA., Roy, S., Valliancourt, J.P., Chapman, K.T. and Nicholson, D.W. (1997) "A combinatorial approach defines specificities of members of the caspase family and granzyme B", J. Biol. Chem. 272, 17907–17911.
   PubMed Web of Science ®Google Scholar
• Xiao, C., Yang, B.F., Asadi, N., Beguinot, F. and Hao, C. (2002) "Tumor necrosis factor-related apoptosis-inducing ligand-induced death-inducing signaling complex and its modulation by c-FLIP and PED/PEA-15 in glioma cells", J. Biol. Chem. 277, 25020–25025.
   PubMed Web of Science ®Google Scholar
• Gouloumet, V, Metivier, D., Stancou, R., Mami-Chouaib, F., Kroemer, G. and Chouaib, S. (2002) "Wild-type p53 induced sensitization of mutant p53 TNF-resistant cells: role of caspase-8 and mitochondria", Cancer Gene Ther. 9, 219–227.
   PubMed Web of Science ®Google Scholar
• Schrantz, N., Blanchart, D.A., Auffredou, MT., Sharma, S., Leca, G. and Vazquez, A. (1999) "Role of caspases and possible involvement of retinoblastoma protein during TGFP-mediated apoptosis of human B lymphocytes", Oncogene 18, 3511–3519.
   PubMed Web of Science ®Google Scholar
• Xu, S.Q. and El-Deiry, W.S. (2000) "p21 (WAF1/C1P1) inhibits initiator caspase cleavage by TRAIL death receptor DR4", Biochem. Biophys. Res. Commun. 269, 179–190.
   PubMed Web of Science ®Google Scholar
• Schrantz, N., Bourgeade, ME, Mouhamad, S., Leca, G., Sharma, S. and Vazquez, A. (2001) "p38-mediated regulation of an Fas-associated death domain protein-independent pathway leading to caspase-8 activation during TGFbeta-induced apoptosis in human Burkitt lymphoma B cells BL41", MoL Biol. Cell 12, 3139–3151.
   PubMed Web of Science ®Google Scholar
• Adams, J.M. and Corz, S. (2001) "Life-or-death decisions by the Bc1-2 protein family", Trends Biochem. Sci. 26, 61–66.
   PubMed Web of Science ®Google Scholar
• Zamzani, N., Brenner, C., Marzo, I., Susin, S.A. and Kroemer, G. (1998) "Subcellular and submitochondrial mode of action of Bcl-2-like oncoproteins", Oncogene 16, 2265–2282.
   PubMed Web of Science ®Google Scholar
• Bernardi, P., Petronili, V, Di Lisa, F. and Forte, M. (2001) "A mitochondrial perspective on cell death", Trends Biochem. Sci. 26, 112–117.
   PubMed Web of Science ®Google Scholar
• Ferri, K.F. and Kroemer, G. (2001) "Organelle-specific initiation of cell death pathways", Nat. Cell Biol. 3, E255—E263.
   PubMed Web of Science ®Google Scholar
• Bratton, S.B., Lewis, J., Butterworth, M., Duckett, C.S. and Cohen, G.M. (2002) "XIAP inhibition of caspase-3 preserves its association with the Apaf-1 apoptosome and prevents CD95- and Bax-induced apoptosis", Cell Death Differ 9, 881–892.
   PubMed Web of Science ®Google Scholar
• Ruiz-Vela, A., Gonzalez de Buitrago, G. and Martinez, A.C. (1999) "Implication of calpain in caspase activation during B cell clonal deletion", EMBO J. 18, 4988–4998.
   PubMed Web of Science ®Google Scholar
• Li, X., Du, L. and Darzynkiewicz, Z. (2000) "During apoptosis of HL-60 and U-937 cells caspases are activated independently of dissipation of mitochondrial electrochemical potential", Exp. Cell Res. 257, 290–297.
   PubMed Web of Science ®Google Scholar
• Slee, E.A., Keogh, S.A. and Martin, S.J. (2000) "Cleavage of BID during cytotoxic drug and UV radiation-induced apoptosis occurs downstream of the point of Bc1-2 action and is catalyzed by caspase-3: a potential feedback loop for amplification of apoptosis-associated mitochondrial cytochrome c release", Cell Death Differ 7, 556–565.
   PubMed Web of Science ®Google Scholar
• Krajewska, M., Zapata, J.M., Meinhold-Heerlein, I., Hedayat, H., Monks, A., Bettendorf, H., Shabaik, A., Bubendorf, L., Kallioniemi, OP., Kim, H., Reifenberger, G., Reed, J.C. and Krajewski, S. (2002) "Expression of bc1-2 family member bid in normal and malignant tissues", Neoplasia 4, 9–140.
   PubMed Web of Science ®Google Scholar
• Zapata, J.M., Takahashi, R., Salvesen, G.S. and Reed, J.C. (1997) "Granzyme release and caspase activation in activated human T-lymphocytes", J. Biol. Chem. 272, 13459–13462.
   PubMed Web of Science ®Google Scholar
• Grabarek, J., Dragan, M., Lee, B.W., Johnson, G.L. and Darzynkiewicz, Z. (2002) "Activation of chymotrypsin-like serine protease(s) during apoptosis detect by affinity-labeling of the enzymatic center with fluoresceinated inhibitor", Intern. J. Oncol. 20, 225–233.
   PubMed Web of Science ®Google Scholar
• Muerkoster, S., Weigand, M.A., Choi, C., Walczak, H., Schirrmacher, V. and Umansky, V. (2002) "Superantigen reactive Vbeta6 + T cells induce perforin/granzyme B mediated caspase-independent apoptosis in tumour cells", Br. J. Cancer 86, 828–836.
   PubMed Web of Science ®Google Scholar
• Rao, R.V., Castro-Obregon, S., Frankowski, H., Schuler, M., Stoka, V, del Rio, G., Bredesen, D.E. and Ellerby, H.M. (2002) "Coupling endoplasmic reticulum stress to the cell death program: an Apaf- 1 -independent intrinsic pathway", J. Biol. Chem. 277, 21836–21842.
   Web of Science ®Google Scholar
• Yoneda, T., Imaizumi, K., Oono, K., Yui, D., Gomi, F., Katayama, T. and Tohyama, M. (2001) "Activation of caspase-12, an endoplasmic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependend mecha-nisms in response to the ER stress", J. Biol. Chem. 276, 13935–13940.
   PubMed Web of Science ®Google Scholar
• Johnson, D.E. (2000) "Noncaspase proteases in apoptosis", Leukemia 14, 1695–1703.
   PubMed Web of Science ®Google Scholar
• Lamothe, B. and Aggarwal, B.B. (2002) "Ectopic expression of Bc1-2 and Bc1-xL inhibits apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL) through suppression of caspases-8, 7, and 3 and BID cleavage in human acute myelogenous leukemia cell line HL-60", J. Interferon Cytokine Res. 22, 269–279.
   PubMed Web of Science ®Google Scholar
• Barry, M., Heibein, J., Pinkoski, M. and Bleackley, R.C. (2000) "Quantitative measurement of apoptosis induced by cytotoxic T lymphocytes", Methods Enzymol. 322, 40–46.
   PubMed Web of Science ®Google Scholar
• Kraemer, G. (1998) "The mitochondrion as an integrator/coordi-nator of cell death pathways", Cell Death Differ. 5, 547–548.
   PubMed Web of Science ®Google Scholar
• Shapiro, H.M. (2000) "Membrane potential estimation by flow cytometry", Methods 21, 271–279.
   PubMed Web of Science ®Google Scholar
• Darzynkiewicz, Z., Traganos, F., Staiano-Coico, L., Kapuscinski, J. and Melamed, M.R. (1992) "Interactions of rhodamine 123 with living cells studied by flow cytometry", Cancer Res. 42, 799–806.
   Google Scholar
• Johnsohn, L.V., Walsh, M.L. and Chen, LB. (1980) "Localisation of mitochondria in living cells with rhodamine 123", Proc. Natl Acad. Sci. 77, 990–994.
   PubMed Web of Science ®Google Scholar
• Darzynkiewicz, Z., Li, X. and Gong, J. (1994) "Assays of cell viability. Discrimination of cells dying by apoptosis", Methods Cell Biol. 41, 16–39.
   Web of Science ®Google Scholar
• Finucane, D.M., Waterhouse, N.J., Amaranto-Mendes, G.P., Cotter, T.G. and Green, D.R. (1999) "Collapse of the inner mitochondrial transmembrane potential is not required for apoptosis of HL-60 cells", Exp. Cell Res. 251, 166–174.
   PubMed Web of Science ®Google Scholar
• Fadok, V.A., Voelker, D.R., Campbell, Pa., et al. (1992) "Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages", J. ImmunoL 142, 2207–2216.
   Google Scholar
• Van Engeland, M., Nieland, L.J.W., Ramaekers, F.C.S., Schutte, B. and Reutelingsperger, P.M. (1998) "Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidyl-serine exposure", Cytometry 31, 1–9.
   PubMedGoogle Scholar
• Darzynkiewicz, Z., Bedner, E. and Smolewski, P. (2001) "Flow cytometry in analysis of cell cycle and apoptosis", Semin. Hematology 38, 179–193.
   PubMed Web of Science ®Google Scholar
• Arends, M.J., Morris, R.G. and Wyllie, A.H. (1990) "Apoptosis: the role of endonuclease", Am. J. PathoL 136, 595–608.
   Web of Science ®Google Scholar
• Kerr, J.F.R., Wyllie, A.H. and Curie, A.R. (1972) "Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics", Br J. Cancer 26, 239–257.
   PubMed Web of Science ®Google Scholar
• Bedner, E., Li, X., Gorczyca, W., Melamed, M.R. and Darzynkiewicz, Z. (1999) "Analysis of apoptosis by laser scanning cytometry", Cytometry 35, 181–195.
   PubMedGoogle Scholar
• Darzynkiewicz, Z., Smolewski, P. and Bedner, E. (2002) "Use of flow and laser scanning cytometry to study mechanisms regulating cell cycle and controlling cell death", HematoL Onc oL Clin. N. Am. 16, 339–355.
   Web of Science ®Google Scholar
• Gong, J., Traganos, F. and Darzynkiewicz, Z. (1994) "A selective procedure for DNA extraction from apoptotic cells applicable for gel electrophoresis and flow cytometry", Ann. Biochem. 218, 314–319.
   Web of Science ®Google Scholar
• Darzynkiewicz, Z., Juan, G., Li, X., Murakami, T. and Traganos, F. (1997) "Cytometry in cell necrobiology: analysis of apoptosis and accidental cell death (necrosis)", Cytometry 27, 1–20.
   PubMedGoogle Scholar
• Gavrieli, Y, Sherman, Y. and Ben-Sasson, S.A. (1992) "Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation", J. Cell. Biol. 119, 493–501.
   PubMed Web of Science ®Google Scholar
• Gorczyca, W., Bruno, S., Darzynkiewicz, R.J., Gong, J. and Darzynkiewicz, Z. (1992) "DNA strand breaks occurring during apoptosis: their early in situ detection by the terminal deoxynucleotidyl transferase and nick translation assays and prevention by serine protease inhibitors", Int. J. OncoL 1, 639–648.
   PubMed Web of Science ®Google Scholar
• Darzynkiewicz, Z., Bedner, E. and Smolewski, P. (2002) "In situ detection of DNA strand breaks in analysis of apoptosis by flow-and laser scanning-cytometry", Methods Mol. Biol. 203, 69–77.
   PubMedGoogle Scholar
• Li, X., Melamed, M.R. and Darzynkiewicz, Z. (1996) "Detection of apoptosis and DNA replication by differential labeling of DNA strand breaks with fluorochromes of different color", Exp. Cell Res. 222, 28–37.
   PubMed Web of Science ®Google Scholar
• Tobey, R.A. (1975) "Different drugs arrest cells at a number of distinct stages in G2", Nature 254, 245–247.
   PubMed Web of Science ®Google Scholar
• Zhang, T.S., Hunort, S., Kuida, K. and Flavell, R.A. (1999) "Caspase knockouts: matters of life and death", Cell Death Differ 6, 1043–1053.
   PubMed Web of Science ®Google Scholar
• Gorman, A.M., Hirt, U.A., Zhivotovsky, B., Orrenius, S. and Ceccatelliu, S. (1999) "Application of a fluorometric assay to detect caspase activity in thymus tissue undergoing apoptosis in vivo", J. ImmunoL Methods 226, 43–48.
   PubMed Web of Science ®Google Scholar
• Liu, J., Bhalgat, M., Zhang, C., Diwu, Z., Hoyland, B. and Klaubert, D.H. (1999) "Fluorescent molecular probes V: a sensitive caspase-3 substrate for fluorometric assays", Bioorg. Med. Chem. Lett. 9, 3231–3236.
   PubMed Web of Science ®Google Scholar
• Martinsson, P., Ekelund, S., Nygren, P. and Larsson, R. (2002) "The combination of antitumoral pyridyl cyanoguanidyne CHS 828 and etoposide in vitro- from cytotoxic synergy to complete inhibition of apoptosis", Br J. PhannacoL 137, 568–573.
   Web of Science ®Google Scholar
• Komoriya, A., Packard, B.Z., Brown, M.J., Wu, M.L. and Henkart, P.A. (2000) "Assessment of caspase activities in intact apoptotic thymocytes using cell-permeable fluorogenic caspase substrates", J. Exp. Med. 191, 1819–1828.
   PubMed Web of Science ®Google Scholar
• Hetz, C.A., Hunn, M., Rojas, P., Tones, V, Leyton, L. and Quest, A.F. (2002) "Caspase-dependent initiation of apoptosis and necrosis by the Fos receptor in lymphoid cells: onset of necrosis is associated with delayed ceramide increase", J. Cell Sci. 115, 4671–4683.
   PubMed Web of Science ®Google Scholar
• Belloc, F., Belaund-Rotureau, M.A., Lavignolle, V, Bascans, E., Braz-Pereira, E., Durrieu, F. and Lacombe, F. (2000) "Flow cytometry of caspase-3 activation in preapoptotic leukemic cells", Cytometry 40, 151–160.
   PubMedGoogle Scholar
• Tanaka, M., Momoi, T. and Marunouchi, T. (2000) "In situ detection of activated caspase-3 in apoptotic granule neurons in the developing cerebellum in slice cultures and in vivo", Brain Res. Dev. Brain Res. 21, 223–228.
   Google Scholar
• Dukers, D.F., Meijer, C.J., ten Berge, R.L., Vos, W., Ossenkoppele, G.J. and Oudejans, J.J. (2002) "High numbers of active caspase 3-positive Reed—Sternberg cells in pretreatment biopsy specimens of patients with Hodgkin disease predict favorable clinical outcome", Blood 100, 36–42.
   PubMed Web of Science ®Google Scholar
• Dukers, D.F., Oudejans, J.J., Vos, W., ten Berge, R.L. and Meijer, C.J. (2002) "Apoptosis in B-cell lymphomas and reactive lymphoid tissues always involves activation of caspase 3 as determined by a new in situ detection method", J. PathoL 196, 307–315.
   PubMed Web of Science ®Google Scholar
• de Murcia, G. and Menissier-de Murcia, J.M. (1994) "Poly (ADP-ribose) polymerase: a molecular nick sensor", Trends Biochem. Sci. 19, 172–176.
   PubMed Web of Science ®Google Scholar
• Lazebnik, Y.A., Kaufmann, S.H., Desnoyers, S., Poirier, G.G. and Earnshaw, W.C. (1994) "Cleavage of poly(ADP-ribose) polymerase by proteinase with properties like ICE", Nature 371, 346–347.
   PubMed Web of Science ®Google Scholar
• Li, X. and Darzynkiewicz, Z. (2000) "Cleavage of poly (ADP-ribose) polymerase measured in situ in individual cells: relationship to DNA fragmentation and cell cycle position during apoptosis", Exp. Cell Res. 255, 125–132.
   PubMed Web of Science ®Google Scholar
• Bedner, E., Smolewski, P., Amstad, P. and Darzynkiewicz, Z. (2000) "Activation of caspases measured in situ by binding of fluorochrome-labeled inhibitors of caspases (FLICA): correlation with DNA fragmentation", Exp. Cell Res. 259, 308–313.
   PubMed Web of Science ®Google Scholar
• Smolewski, P., Bedner, E., Du, L., Hsieh, T.C., Wu, J.M., Phelps, D.J. and Darzynkiewicz, Z. (2001) "Detection of caspases activation by fluorochrome-labeled inhibitors: multiparameter analysis by laser scanning cytometry", Cytometry 44, 73–82.
   PubMedGoogle Scholar
• Szmigielska-Kaplon, A., Smolewski, P., Najder, M. and Robak, T. (2002) "Evaluation of apoptosis induced in vitro by cladribine (2-CdA) combined with anthracyclines in lymphocytes from patients with B-cell chronic lymphocytic leukemia", Ann. HematoL 81, 508–513.
   PubMed Web of Science ®Google Scholar
• Darzynkiewicz, Z. and Barnard, E.A. (1966) "Specific proteases of mast cells", Nature 212, 1198–1203.
   PubMed Web of Science ®Google Scholar
• Smolewski, P., Grabarek, J., Halicka, H.D. and Darzynkiewicz, Z. (2002) "Assay of caspases activation in situ combined with probing plasma membrane integrity detects three distinct stages of apoptosis", J. Immunol. Methods 265, 111–121.
   PubMed Web of Science ®Google Scholar
• Kerr, J.F.R., Winterford, C.M. and Harmon, V. (1994) "Apoptosis. Its significance in cancer and cancer therapy", Cancer 73, 2013–2026.
   PubMed Web of Science ®Google Scholar
• Vaux, D.L. and Korsmayer, S.J. (1999) "Cell death in development", Cell 96, 245–254.
   PubMed Web of Science ®Google Scholar
• Li, X., Gong, J., Feldman, E., Seiter, K., Traganos, F. and Darzynkiewicz, Z. (1994) "Apoptotic cell death during treatment of leukemias", Leuk. Lymphoma 13, 65–72.
   PubMed Web of Science ®Google Scholar
• Seiter, K., Feldman, E.J., Halicka, H.D., Traganos, F., Darzynkiewicz, Z., Lake, D. and Ahmed, T. (1997) "Phase I clinical and laboratory evaluation of topotecan and cytarabine in patients with acute leukemia", J. Clin. Oncol. 15, 44–51.
   PubMed Web of Science ®Google Scholar
• Seiter, K., Feldman, EL, Traganos, F., et al. (1995) "Evaluation in vivo induction of apoptosis in patients with acute leukemia treated on a phase I study with Paclitaxel", Leukemia 9, 1851–1856.
   PubMed Web of Science ®Google Scholar
• Darzynkiewicz, Z., Bedner, E. and Traganos, F. (2001) "Difficulties and pitfalls in analysis of apoptosis", Methods Cell Biol. 263, 527–546.
   Google Scholar
• Darzynkiewicz, Z., Juan, G., Li, X., Murakami, T. and Traganos, F. (1997) "Cytometry in cell necrobiology: analysis of apoptosis and accidental cell death (necrosis)", Cytometry 27, 1–20.
   PubMedGoogle Scholar
• Ormerod, M.G. (1998) "The study of apoptotic cells by flow cytometry", Leukemia 12, 1013–1025.
   PubMed Web of Science ®Google Scholar
• Smolewski, P., Grabarek, J., Phelps, D.J. and Darzynkiewicz, Z. (2001) "Stathmo-apoptosis: arresting apoptosis by fluorochrome-labeled inhibitor of caspases", Int. J. Oncol. 19, 657–663.
   PubMed Web of Science ®Google Scholar
• Smolewski, P., Grabarek, J. and Darzynkiewicz, Z. (2002) "Kinetics of HL-60 cell entrance to apoptosis during treatment with TNF-alfa or camptotecin assayed by the stathmoapoptosis method", Cytometry 47, 143–149.
   PubMedGoogle Scholar
• Lin, C.W., Manshouri, T., Jilani, I., Neuberg, D., Patel, K., Kantarjian, H., Andreeff, M., Estrov, Z., Beran, M., Keating, M., Estey, E. and Albitar, M. (2002) "Proliferation and apoptosis in acute and chronic leukemias and myelodysplastic syndrome", Leuk. Res. 26, 551–559.
   PubMed Web of Science ®Google Scholar
• Liu, L., Eby, M., Rathore, N., Sinke, S.K., Kumar, A. and Chaudhary, P.M. (2002) "The human herpes virus8-encoded viral FLICE inhibitory protein physically associated with and persistently activates the flcappa B kinase complex", J. Biol. Chem. 277, 13745–137451.
   PubMed Web of Science ®Google Scholar
• Gaide, 0., Martinon, F., Micheau, 0., Bonnet, D., Thome, M. and Tschopp, J. (2001) "Carmal, a CARD-containing binding partner of Bc110, induces phosphorylation and NF-kappaB activation", FEBS Lett. 496, 121–127.
   PubMed Web of Science ®Google Scholar
• Schneider, C. and Hiibinger, G. (2002) "Pleiotropic signal transduction mediated by human CD30: a member of the tumor necrosis factor receptor (TNFR) family", Leuk. Lymphoma 43, 1355–1366.
   PubMed Web of Science ®Google Scholar
• Snow, AL., Chen, L.J., Nepomuceno, R.R., Krams, S.M., Esquivel, C.O. and Martinez, O.M. (2001) "Resistance to Fas-mediated apoptosis in EBV-infected B cell lymphomas is due to defects in the proximal Fas signaling", J. Immunol. 167, 5404–5411.
   PubMed Web of Science ®Google Scholar
• Dales, J.P., Palmerini, F., Devilard, E., Hassoun, J., Birg, F. and Xerri, L. (2001) "Caspases: conductors of the cell death machinery in lymphoma cells", Leuk. Lymphoma 41, 247–253.
   PubMed Web of Science ®Google Scholar
• Serafeim, A., Grafton, G., Chamba, A., Gregory, C.D., Blakely, RD., Bowery, N.G., Barnes, N.M. and Gordon, J. (2002) "5-Hydroxytryptamine drives apoptosis in biopsylike Burkitt lymphoma cells: reversal by selective serotonin reuptake inhibitors", Blood 99, 2545–2553.
   PubMed Web of Science ®Google Scholar
• Schrantz, N., Auffredou, M.T., Bourgeade, ME, Besnault, L., Leca, G. and Vazquez, A. (2001) "Zinc-mediated regulation of caspases activity: dose-dependent inhibition or activation of caspase-3 in the human Burkitt lymphoma B cells (Ramos)", Cell Death Differ 8, 152–161.
   PubMed Web of Science ®Google Scholar
• Besnault, I., Schrantz, N., Auffredou, M.T., Leca, G., Bourgeade, M.F. and Vazquez, A. (2001) "B cell cross-linking triggers a caspase-8-dependent apoptotic pathway that is independent of the death effector domain of Fas-associated death domain protein", J. Immunol. 167, 733–740.
   PubMed Web of Science ®Google Scholar
• Herold, M.J., Kuss, A.W., Kraus, C. and Berberich, I. (2002) "Mitochondria-dependent caspase-9 activation is necessary for antigen receptor-mediated effector caspase activation and apoptosis in WEHI 231 lymphoma cells", J. Immunol. 168, 3902–3909.
   PubMed Web of Science ®Google Scholar
• Armstrong, IS., Hornung, B., Lecane, P., Jones, D.P. and Knox, S.J. (2001) "Rotenone-induced G2/M cell cycle arrest and apoptosis in a human B lymphoma cell line PW", Biochem. Biophys. Res. Commun. 289, 973–978.
   PubMed Web of Science ®Google Scholar
• Totth, A., Sebestyen, A., Barna, G., Nagy, K., Gondor, A., Bocsi, J., Mihalik, R., Petak, I., Houghton, J. and Kopper, L. (2001) "TGF beta 1 induces caspase-dependent but death-receptor independent apoptosis in lymphoid cells", Anti Cancer Res. 21, 1207–1212.
   PubMed Web of Science ®Google Scholar
• Jiang, A. and Clark, E.A. (2001) "Involvement of Bik, a proapoptotic member of the Bc1-2 family, in surface IgM-mediated B-cell apoptosis", J. Immunol. 166, 6025–6033.
   PubMed Web of Science ®Google Scholar
• Schaich, M. and Elmer, T. (2002) "Mdrl gene expression and mutations in Ras proto-oncogenes in acute myeloid leukemia", Leuk. Lymphoma 43, 1345–1354.
   PubMed Web of Science ®Google Scholar
• Kappelmayer, J., Karashi, E., Telek and Jakab, K. (2002) "Pros and cons on how to measure multidrug resistance in leukemias", Leuk. Lymphoma 43, 711–717.
   PubMed Web of Science ®Google Scholar
• ten Berge, R.L., Meijer, C.J., Dukers, D.F., Kummer, J.A., Bladergreon, B.A., Vos, W., Hack, C.E., Ossenkoppele, G.J. and Oudejans, J.J. (2002) "Expresions levels of apoptosis-related proteins predict clinical outcome in anaplastic large cell lymphoma", Blood 99, 4540–4546.
   PubMed Web of Science ®Google Scholar
• Suvas, S., Singh, V, Sahdev, S., Vohra, H. and Agrewala, J.N. (2002) "Distinct role of CD80 and CD86 in the regulation of the activation of B cell and B cell lymphoma", J. Biol. Chem. 277, 7766–7775.
   PubMed Web of Science ®Google Scholar
• Keating, M.J. (1999) "Chronic lymphocytic leukemia", Semin. Oncol. 26\(Suppl. 14), 107–114.
   PubMed Web of Science ®Google Scholar
• King, D., Pringle, J.H., Hutchinson, M. and Cohen, G.M. (1998) "Processing/activation of caspases, -3 and -7 and -8 but not caspase-2, in the induction of apoptosis in B-chronic lymphocytic leukemia cells", Leukemia 12, 1553–1560.
   PubMed Web of Science ®Google Scholar
• Stoetzer, 0.J., Pogrebniak, A., Scholz, M., Pelka-Fleischer, R., Gullis, E., Darsow, M., Nussler, V. and Wilmanns, W. (1999) "Drug-induced apoptosis in chronic lymphocytic leukemia", Leukemia 13, 1873–1880.
   Google Scholar
• Jones, D.T., Ganeshaguru, K., Virchis, A.E., Folarin, NI., Lowdell, M.W., Mehta, A.B., Prentice, H.G., Hoffbrand, A.V. and Wickremasinghe, R.G. (2001) "Caspase 8 activation independent of Fos (CD95/AP0-1) signaling may mediate killing of B-chronic lymphocytic leukemia cells by cytotoxic drugs or gamma radiation", Blood 98, 2800–2807.
   PubMed Web of Science ®Google Scholar
• Bellosillo, B., Villamor, N., Lopez-Guillermo, A., Marce, S., Bosch, F., Campo, E., Montserrat, E. and Colomer, D. (2002) "Spontaneous and drug-induced apoptosis is mediated by conformational changes of Box and Bak in B-cell chronic lymphocytic leukemia", Blood 100, 1810–1816.
   PubMed Web of Science ®Google Scholar
• Wall, N.R., Beck, F.W., Al-Katib, AM. and Mohammad, R.M. (2001) "Treatment-induced expression of anti-apoptotic proteins in WSU-CLL, a human chronic lymphocytic leukemia cell line", J. Drug Target. 9, 329–339.
   Web of Science ®Google Scholar
• Chandra, J., Mansson, E., Gogvadze, V, Kaufmann, S.H., Albertoni, F. and Orrenius, S. (2002) "Resistance of leukemic cells to 2-chlorodeoxyadenosisne is due to a lack of calcium-dependent cytochrome c release", Blood 99, 655–663.
   PubMed Web of Science ®Google Scholar
• Pedersen, I.M., Kitada, S., Schimmer, A., Kim, Y., Zapata, J.M., Charboneau, L., Rassenti, L., Andreeff, M., Bennett, F., Sporn, Liotta, L.D., Kipps, T.J. and Reed, J.C. (2002) "The triterpenoid CDDO induces apoptosis in refractory CLL B cells", Blood 100, 2965–2972.
   PubMed Web of Science ®Google Scholar
• MacFarlane, M., Harper, N., Snowden, R.T., Dyer, M.J., Barnett, G.A., Pringle, J.H. and Cohen, G.M. (2002) "Mechanisms of resistance to TRAIL-induced apoptosis in primary B cell chronic lymphocytic leukaemia", Oncogene 21, 6809–6818.
   PubMed Web of Science ®Google Scholar
• Min, R., Li, Z., Epstein, J., Barlogie, B. and Yi, Q. (2002) "Beta(2)-microglobulin as a negative growth regulator of myeloma cells", Br J. Haematol. 118, 495–505.
   PubMed Web of Science ®Google Scholar
• Pene, F., Claessens, YE., Muller, 0., Viguie, F., Mayeux, P., Dreyfus, F., Lacombe, C. and Bouscary, D. (2002) "Role of the phosphatidylinositol 3-kinase/Akt and mTOR/P70S6-kinase path-ways in the proliferation and apoptosis in multiple myeloma", Oncogene 21, 6587–6597.
   Google Scholar
• Hideshima, T., Mitsiades, C., Akiyama, M., Hayashi, T., Chauhan, D., Richardson, P., Schlossman, R., Podar, K., Munshi, N.C., Mitsiades, N. and Anderson, K.C. (2002) "Molecular mechanisms mediating anti-myeloma activity of proteasome inhibitor PS-341", Blood Sep 26, In press.
   Google Scholar
• Minami, R., Muta, K., Ilseung, C., Abe, Y, Nishimura, J. and Nawata, H. (2000) "Interleukin-6 sensitizes multiple myeloma cell lines for apoptosis induced by interferon-alpha", Exp. Hematol. 28, 244–255.
   PubMed Web of Science ®Google Scholar
• Choi, Y., Zhang, J., Murga, C., Yu, H., Koller, E., Monia, B.P., Gutkind, J.S. and Li, W. (2002) "PTEN, but not SHIP and SHIP2, suppresses the PI3K/Akt pathway and induces growth inhibition and apoptosis of myeloma cells", Oncogene 21, 5289–5300.
   PubMed Web of Science ®Google Scholar
• Chauhan, D., Catley, L., Hideshima, T., Li, G., Leblanc, R., Gupta, D., Sattler, M., Richardson, P., Schlossman, R.L., Podar, K., Weller, E., Munshi, N. and Anderson, K.C. (2002) "2-Methoxy-estradiol overcomes drug resistance in multiple myeloma cells", Blood 100, 2187–2194.
   PubMed Web of Science ®Google Scholar
• Chauhan, D., Hideshima, T., Rosen, S., Reed, J.C., Kharbanda, S. and Anderson, K.C. (2001) "Apaf-l/cytochrome c-independent and Smac-dependent induction of apoptosis in multiple myeloma (MM) cells", J. Biol. Chem. 276, 24453–24456.
   PubMed Web of Science ®Google Scholar
• Chen, Q., Gong, B., Mahmoud-Ahmed, AS., Thou, A., Hsi, E.D., Hussein, M. and Almasan, A. (2001) "Apo2L/TRA1L and Bc1-2-related proteins regulate type I interferon-induced apoptosis in multiple myeloma", Blood 98, 2183–2192.
   PubMed Web of Science ®Google Scholar
• Chen, Q., Gong, B. and Almasan, A. (2000) "Distinct stages of cytochrome c release from mitochondria: evidence for a feedback amplification loop linking caspase activation to mitochondrial dysfunction in genotoxic stress induced apoptosis", Cell Death Differ 7, 227–233.
   PubMed Web of Science ®Google Scholar
• Mitsiades, N., Mitsiades, CS., Poulald, V, Chauhan, D., Richardson, P.G., Hideshima, T., Munshi, N.C., Treon, SY. and Anderson, K.C. (2002) "Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications", Blood 99, 4525–4530.
   PubMed Web of Science ®Google Scholar
• Gupta, D., Podar, K., Tai, Y.T., Lin, B., Hideshima, T., Aldyama, M., LeBlanc, R., Catley, L., Mitsiades, N., Mitsiades, C., Chauhan, D., Munshi, N.C. and Anderson, K.C. (2002) "Beta-lapachone, a novel plant product, overcomes drug resistance in human multiple myeloma cells", Exp. Hematol. 30, 711–720.
   PubMed Web of Science ®Google Scholar
• Frassanito, M.A., Cusmai, A., Piccoli, C. and Dammacco, F. (2002) "Manumycin inhibits farnesyltransferase and induces apoptosis of drug-resistant interleukin 6-producing myeloma cells", Br J. Haematol. 118, 157–165.
   PubMed Web of Science ®Google Scholar
• Mitsiades, N., Mitsiades, CS., Poulaki, V, Anderson, K.C. and Treon, S.P. (2001) "Concepts in the use of TRAIL/Apo2L: an emerging biotherapy for myeloma and other neoplasias", Expert Opin. Investig. Drugs 10, 1521–1530.
   PubMed Web of Science ®Google Scholar
• Jazirehi, A.R., Ng, C.P., Gan, X.H., Schiller, G. and Bonavida, B. (2001) "Adriamycin sensitizes the adriamycin-resistant 8226/Dox40 human multiple myeloma cells to Apo2L/tumor necrosis factor-related apoptosis-inducing ligand-mediated (TRAIL) apoptosis", Clin. Cancer Res. 7, 3874–3883.
   PubMed Web of Science ®Google Scholar
• Jia, P., Chen, G., Huang, X., Cai, X., Yang, J., Wang, L., Thou, Y., Shen, Y, Thou, L., Yu, Y, Chen, S., Zhang, X. and Wang, Z. (2001) "Arsenic trioxide induces multiple myeloma cell apoptosis via disruption of mitochondrial transmembrane potentials and activation of caspase-3", Chin. Med. J. 114, 19–24.
   PubMed Web of Science ®Google Scholar
• Gartenhaus, R.B., Prachand, S.N., Paniaqua, M., Li, Y. and Gordon, L.I. (2002) "Arsenic trioxide cytotoxicity in steroid and chemotherapy-resistant myeloma cell lines: enhancement of apoptosis by manipulation of cellular redox state", Clin. Cancer Res. 8, 566–572.
   PubMed Web of Science ®Google Scholar
• Oliver, L., Vavasseur, F., Mahe, B., Perrin, P., Harousseau, J.L., Meflah, K. and Vallette, F.M. (2002) "Assessment of caspase activity as a possible prognostic factor in acute myeloid leukaemia", Br J. Haematol. 118, 434–437.
   PubMed Web of Science ®Google Scholar
• Hirst, W., Buggins, A. and Mufti, G. (2002) "Central role of leukemia-derived factors in the development of leukemia-associated immune dysfunction", Hematol. J. 2, 2–17.
   Google Scholar
• Svingen, RA., Tefferi, A., Kottke, T.J., Kaur, G., Narayanan, V.L., Sausville, E.A. and Kaufmann, S.H. (2000) "Effects of the bcr/abl kinase inhibitors AG957 and NSC 680410 on chronic myelo-genous leukemia cells in vitro", Clin. Cancer Res. 6, 237–249.
   PubMed Web of Science ®Google Scholar
• Campos, L, Sabido, 0., Viallet, A., Vasselon, C. and Guyotat, D. (1999) "Expression of apoptosis-controlling proteins in acute leukemia cells", Leuk. Lymphoma 33, 499–509.
   Google Scholar
• Belaud-Rotureau, M.A., Durrieu, F., Labroille, G., Lacombe, F., Fitoussi, 0., Agape, P., Marit, G., Reiffers, J. and Belloc, F. (2000) "Study of apoptosis-related responses of leukemic blast cells to in vitro anthracycline treatment", Leukemia 14, 1266–1275.
   PubMed Web of Science ®Google Scholar
• Dunusii-Joannopoulos, K. (2002) "The combination of che-motherapy and systemic immunotherapy and the concept of cure in murine Leuk. Lymphoma", Leuk. Lymphoma 43, 2075–2082.
   PubMed Web of Science ®Google Scholar
• Boudard, D., Sordet, 0., Vasselon, C., Revol, V, Bretheas, M.F., Freyssenet, D., Viallet, A., Piselli, S. and Guyotat, D. (2000) "Expression and activity of caspases 1 and 3 in myelodysplastic syndromes", Leukemia 14, 2045–2051.
   Google Scholar
• Lin, C.W., Manshouri, T., Jilani, I., Neuberg, D., Patel, K., Kantarjian, H., Andreeff, M., Estrov, Z., Beran, M., Keating, M., Estey, E. and Albitar, M. (2002) "Proliferation and apoptosis in acute and chronic leukemias and myelodysplastic syndrome", Leuk. Res. 26, 551 —559.
   PubMed Web of Science ®Google Scholar
• Claessens, YE., Bouscary, D., Dupont, J.M., Picard, E, Melle, J., Gisselbrecht, S., Lacombe, C., Dreyfus, F., Mayeux, P. and Fontenay-Roupie, M. (2002) "In vitro proliferation and differen-tiation of erythroid progenitors from patients with myelopdyplas-tic syndromes: evidence for Fas-dependent apoptosis", Blood 99, 1594–1601.
   Google Scholar
• Boudard, D., Vasselon, C., Bretheas, M.F., Jaubert, J., Mournier, C., Reynaud, J., Viallet, A., Chautard, S., Guyotat, D. and Campos, L. (2002) "Expression and prognostic significant of Bc1-2 family proteins myelodysplastics syndromes", Am. J. Hematol. 70, 115–125.
   PubMed Web of Science ®Google Scholar
• Zang, Y, Goodwin, R.G., Loken, MR., Bryant, E. and Deeg, J. (2001) "Expression of tumor necrosis factor-mediated apoptosis-inducing ligand, Apo2L, and its receptors in myelodysplastic syndrome: effects on in vitro hemopoiesis", Blood 98, 3058–3065.
   PubMed Web of Science ®Google Scholar
• Daley, G.Q., Van Etten, R.A. and Baltiomore, D. (1990) "Blast crisis in a murine model of chronic myelogenous leukemia", Science 247, 824–830.
   PubMed Web of Science ®Google Scholar
• Lugo, T.C., Pendergarst, A.M., Muller, A.J. and Witte, ON. (1990) "Tyrosine kinase activity and transformation potency of bcr-abl oncogene products", Science 247, 1079–1082.
   PubMed Web of Science ®Google Scholar
• Dan, S., Naito, M., Seimiya, H., Kizaki, A., Mashima, T. and Tsunio, T. (1999) "Activation of c-Abl tyrosine kinase requires caspase activation and is not involved in JNK/SAPK activation during apoptosis of human monocytic leukemia U937 cells", Oncogene 18, 1277–1283.
   PubMed Web of Science ®Google Scholar
• Dan, S., Naito, M. and Tsuruo, T. (1998) "Selective induction of apoptosis in Philadelphia chromosome-positive chronic myelogenous leukemia cells by an inhibitor of BCR—ABL tyrosine kinase, CGP 57148", Cell Death Differ 5, 710–715.
   PubMed Web of Science ®Google Scholar
• Oetzel, C., Jonuleit, T., Gotz, A., van der Kuip, H., Michels, H., Duyster, J., Hallek, M. and Aulitzky, W.E. (2000) "The tyrosine kinase inhibitor CGP 57148 (ST1 571) induces apoptosis in BCR-ABL-positive cells by down-regulating BCL-X", Clin. Cancer Res. 6, 1958–1968.
   PubMed Web of Science ®Google Scholar
• Druker, B.J., Sawyers, CL., Kantarijan, H., Resta, D.J., Reese, S.F., Ford, J.M., Capdeville, R. and Talpaz, M. (2001) "Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome", N. Engl. J. Med. 344, 1038–1042.
   PubMed Web of Science ®Google Scholar
• Druker, B.J., Talpaz, M., Resta, D.J., Peng, B., Buchdunger, E., Ford, J.M., Lydon, N.B., Kantarijan, H., Capdeville, R., Ohno-Jones, S. and Sawyers, C.L. (2001) "Efficiacy and safety of a specific inhibitor BCR-ABL tyrosine kinase in chronic myeloid leukemia", N. Engl. J. Med. 344, 1031–1037.
   PubMed Web of Science ®Google Scholar
• Klejman, A., Rushen, L., Morrione, A., Slupianek, A. and Skorski, T. (2002) "Phosphatidylinosito1-3 kinase inhibitors enhance the anti-leukemia effect of ST1571", Oncogene 21, 5868–5876.
   PubMed Web of Science ®Google Scholar
• Shim, M.J., Kim, H.J., Yang, S.J., Lee, I.S., Choi, H.I. and Kim, T. (2002) "Arsenic trioxide induces apoptosis in chronic myelo-genous leukemia K562 cells: possible involvement of p38 MAP kinase", J. Biochem. MoL Biol. 35, 377–383.
   PubMedGoogle Scholar
• La Rosee, P., Johnson, K., O'Dwyer, M.E. and Druker, B.J. (2002) "In vitro studies of the combination of imatinib mesylate (Gleevec) and arsenic trioxide (Trisenox) in chronic myelogenous leukemia", Exp. Hematol. 30, 729–737.
   PubMed Web of Science ®Google Scholar
• Gangemi, R.M., Santamaria, B., Bargellesi, A., Cosulich, E. and Fabbi, M. (2000) "Late apoptotic effects of taxanes on K562 erythroleukemia cells: apoptosis is delayed upstream of caspase-3 activation", Intern. J. Cancer 85, 527–533.
   PubMed Web of Science ®Google Scholar
• Mc Gee, MM., Campiani, G., Ramunno, A., Fattorusso, C., Nacci, V., Lawler, M., Williams, D.C. and Zisterer, D.M. (2001) "Pyrrolo-1,5-benzoxazepines induce apoptosis in chronic myelogenous leukemia (CML) cells by bypassing the apoptotic suppressor bcr-abl", J. Phannacol. Exp. Ther. 296, 31–40.
   PubMed Web of Science ®Google Scholar
• Wu, J., Suzuki, H., Thou, Y.W., Liu, W., Yoshihara, M., Kato, M., Akhand, A.A., Hayakawa, A., Takeuchi, K., Hossain, K., Kurosawa, M. and Nakashima, I. (2001) "Cepharanthine activates caspases and induces apoptosis in Jurkat and K562 human leukemia cell lines", J. Cell. Biochem. 82, 200–214.
   PubMed Web of Science ®Google Scholar
• Clodi, K., Kliche, K.O., Zhao, S., Weidner, D., Schenk, T., Consoli, U., Jiang, S., Snell, V. and Andreeff, M. (2000) "Cell-surface exposure of phosphatidylserine correlates with the stage of fludarabine-induced apoptosis in chronic lymphocytic leukemia and expression of apoptosis-regulating genes", Cytometry 40, 19–25.
   PubMedGoogle Scholar
• Chow, K.U., Rummel, M.J., Weichmann, E., Ries, J., Jantschke, P., Boehrer, S., Pourebrahim, F., Napieralski, S., Stein, J., Martin, H., Hoelzer, D. and Mitron, P.S. (2000) "Induction of apoptosis by 2-chloro2-deoxyadenosine (2-CdA) alone and in combination with other cytostatic drugs: synergistic effect on normal and neoplastic lymphocytes by addition of doxorubicin and mitoxantrone", Leuk. Lymphoma 36, 559–567.
   PubMed Web of Science ®Google Scholar
• Bellosillo, B., Colomer, D., Pons, G. and Gil, J. (1998) "Mitoxantrone, a topoisomerase 11 inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells", Br J. Haematol. 100, 142–146.
   PubMed Web of Science ®Google Scholar
• Robak, T. (2001) "Cladribine in the treatment of chronic lymphocytic leukemia", Leuk. Lymphoma 40, 551–564.
   PubMed Web of Science ®Google Scholar
• Genini, D., Budihardjo, I., Plunkett, W., Wang, X., Carrera, C.J., Cottam, H.B., Carson, D.A. and Leoni, L.M. (2000) "Nucleotide requirements for the in vitro activation of the apoptosis protein-activating factor-1 -mediated caspase pathway", J. Biol. Chem. 275, 29–34.
   PubMed Web of Science ®Google Scholar
• Marzo, I., Perez-Galan, P., Giraldo, P., Rubio-Felix, D., Anel, A. and Naval, J. (2001) "Cladribine induces apoptosis in human leukemia cells by caspase-dependent and -independent pathways acting on mitochondria", Biochem. J. 359, 537–546.
   PubMed Web of Science ®Google Scholar
• Van Den Neste, E., Cardoen, S., Husson, B., Rosier, J.F., Delacauw, A., Ferrant, A., Van den Berghe, G. and Bontemps, F. (2002) "2-Chloro-2'-deoxyadenosine inhibits DNA repair syn-thesis and potentiates UVC cytotoxicity in chronic lymphocytic leukemia B lymphocytes", Leukemia 16, 36–43.
   PubMed Web of Science ®Google Scholar
• Coiffier, B. (2002) "Rituximab in the treatment of diffuse large B-cell lymphomas", Semin. Oncol. 29\(Suppl. 2), 30–35.
   PubMed Web of Science ®Google Scholar
• Keating, M.J., O'Brien, S. and Albitar, M. (2002) "Emerging information on the use of rituximab in chronic lymphocytic leukemia", Semin. Oncol. 29\(Suppl. 2), 70–74.
   Google Scholar
• Alas, S., Ng, C.P. and Bonavida, B. (2002) "Rituximab modifies the cisplatin-mitochondrial signaling pathway, resulting in apoptosis in cisplatin-resistant non-Hodgkin's lymphoma", Clin. Cancer Res. 8, 836–845.
   PubMed Web of Science ®Google Scholar
• Bellosillo, B., Villamor, N., Lopez-Guillermo, A., Marce, S., Esteve, J., Campo, E., Colomer, D. and Montserrat, E. (2001) "Complement-mediated cell death induced by rituximab in B-cell lymphoproliferative disorders is mediated in vitro by a caspase-independent mechanism involving the generation of reactive oxygen species", Blood 98, 2771–2777.
   PubMed Web of Science ®Google Scholar
• Chow, K.U., Sonamerlad, W.D., Boehrer, S., Schneider, B., Seipelt, G., Rummel, M.J., Hoelzer, D., Mitrou, P.S. and Weidmann, E. (2002) "Anti-CD20 antibody (1DEC-C2B8, rituximab) enhances efficacy of cytotoxic drugs on neoplastic lymphocytes in vitro: role of cytokines, complement, and caspases", Haematologica 87, 33–43.
   PubMed Web of Science ®Google Scholar
• Byrd, IC., Kitada, S., Flinn, LW., Aron, J.L., Pearson, M., Lucas, D. and Reed, J.C. (2002) "The mechanism of tumor cell clearance by rituximab in vivo in patients with B-cell chronic lymphocytic leukemia: evidence of caspase activation and apoptosis induc-tion", Blood 99, 1038–1043.
   PubMed Web of Science ®Google Scholar
• Smolewski, P., Szmigielska-Kaplon, A., Cebula, B., Sobczak, A., Darzynldewicz, Z. and Robak, T. (2002) "Pro-apoptotic effect of rituximab alone or in combination with purine nucleoside analogues on B-CLL chronic lymphocytic leukemia cells measured by fluorochrome labeled inhibitors of caspases (FLICA) assay", Blood 100 (abstr.), 1503, 2002 Annual Meeting of the American Society of Hematology, December 2002.
   Google Scholar
• Shan, D., Gopal, A.K. and Press, 0.W. (2001) "Synergistic effects of the fenretinide (4-HPR) and anti-CD20 monoclonal antibodies on apoptosis induction of malignant human B cells", Clin. Cancer Res. 7, 2490–2495.
   PubMed Web of Science ®Google Scholar
• Mateo, V., Lagneaux, L., Bron, D., Biron, G., Armant, M., Delespesse, G. and Sarfati, M. (1999) "CD47 ligation induces caspase-independent cell death in chronic lymphocytic leukemia", Nat. Med. 5, 1277–1284.
   PubMed Web of Science ®Google Scholar
• Chu, P., Wierda, W.G. and Kipps, T.J. (2000) "CD40 activation does not protect chronic lymphocytic leukemia B cells from apoptosis induced by cytotoxic T lymphocytes", Blood 95, 3853–3858.
   PubMed Web of Science ®Google Scholar
• Chu, P., Deforce, D., Pedersen, I.M., Kim, Y, Kitada, S., Reed, J.C. and Kipps, T.J. (2002) "Latent sensitivity to Fas-mediated apoptosis after CD40 ligation may explain activity of CD154 gene therapy in chronic lymphocytic leukemia", Proc. Natl Acad. Sci. USA 99, 3854–3859.
   PubMed Web of Science ®Google Scholar
• Almond, J.B., Snowden, R.T., Hunter, A., Dinsdale, D., Cain, K. and Cohen, G.M. (2001) "Proteasome inhibitor-induced apoptosis of B-chronic lymphocytic leukaemia cells involves cytochrome c release and caspase activation, accompanied by formation of an approximately 700 kDa Apaf-1 containing apoptosome complex", Leukemia 15, 1388–1397.
   PubMed Web of Science ®Google Scholar
• Lagneaux, L., Delforge, A., Cartier, S., Massy, M., Bernier, M. and Bron, D. (2001) "Early induction of apoptosis in B-chronic lymphocytic leukaemia cells by hydroxychloroquine: activation of caspase-3 and no protection by survival factors", Br. J. Haematol. 112, 344–352.
   PubMed Web of Science ®Google Scholar
• Nabha, S.M., Mohammad, R.M., Dandashi, M.H., Coupaye-Gerard, B., Aboukameel, A., Pettit, G.R. and Al-Katib, A.M. (2002) "Combretastatin-A4 prodrug induces mitotic catastrophe in chronic lymphocytic leukemia cell line independent of caspase activation and poly(ADP-ribose)polymerase cleavage", Clin. Cancer Res. 8, 2735–2741.
   PubMed Web of Science ®Google Scholar
• Sievers, E.L. (2001) "Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse", Expert Opin. Biol. Ther. 1, 893–901.
   PubMed Web of Science ®Google Scholar
• Sievers, E.L., Larson, R.A., Stadtmauer, E.A., Estey, E., Lowenberg, B., Dombret, H., Karanes, C., Theobald, M., Bennett, J.M., Sherman, M.L., Berger, US., Eten, C.B., Loken, M.R., van Dongen, J.J., Bernstein, ID. and Appelbaum, F.R. (2001) "Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse", J. Clin. Oncol. 19, 3244–3254.
   PubMed Web of Science ®Google Scholar
• Verma, A. and Platanias, L.C. (2002) "Signalling via the interferon-a receptor in chronic myelogenous leukemia cells", Leuk. Lymphoma 43, 703–709.
   PubMed Web of Science ®Google Scholar
• Voutsadakis, I.A. (2000) "Interferon-alpha and the pathogenesis of myeloproliferative disorders", Med. Oncol. 17, 249–257.
   PubMed Web of Science ®Google Scholar
• Ben Jilani, K.E., Akarid, K., Arnoult, D., Petit, F., Baert, E., Gaillard, J.P., Ameisen, J.C. and Estaquier, J. (2001) "Gamma-interferon induces apoptosis of the B lymphoma WM-279 cell line through a CD95/CD95L-independent mechanism", Eur. Cytokine Network 12, 587–596.
   PubMed Web of Science ®Google Scholar
• Distelhorst, C.W. (2002) "Recent insights into the mechanism of glucocorticosteroid-induced apoptosis", Cell Death Differ 9, 6–19.
   PubMed Web of Science ®Google Scholar
• Ergin, M., Denning, M.F., Izban, K.F., Amin, H.M., Martinez, R.L., Saeed, S. and Alkan, S. (2001) "Inhibition of tyrosine kinase activity induces caspase-dependent apoptosis in anaplastic large cell lymphoma with NPM-ALK (p80) fusion protein", Exp. HematoL 29, 1082–1090.
   PubMed Web of Science ®Google Scholar
• Lovborg, H., Martinsson, P., Gullbo, J., Ekelund, S., Nygren, P. and Larsson, R. (2002) "Modulation of pyridyl cyanoguanidine (CHS 828) induced cytotoxicity by 3-aminobenzamide in U-937 GTB cells", Biochem. Phannacol. 63, 1491–1498.
   PubMed Web of Science ®Google Scholar
• Heimli, H., Giske, C., Naderi, S., Drevon, CA. and Hollungm, K. (2002) "Eicosapentaenoic acid promotes apoptosis in Ramos cells via activation of caspase-3 and -9", Lipids 37, 797–802.
   PubMed Web of Science ®Google Scholar
• Wieder, T., Prokop, A., Bagci, B., Essmann, F., Bernicke, D., Schulze-Osthoff, K., Dorken, B., Schmalz, HG., Daniel, RT. and Henze, G. (2001) "Piceatannol, a hydroxylated analog of the chemopreventive agent resveratrol, is a potent inducer of apoptosis in the lymphoma cell line BJAB and in primary, leukemic lymphoblasts", Leukemia 15, 1735–1742.
   PubMed Web of Science ®Google Scholar
• Fujino, M., Li, X.K., Kitazawa, Y, Guo, L., Kawasaki, M., Funeshima, N., Amano, T. and Suzuki, S. (2002) "Distinct pathways of apoptosis triggered by FTY720, etoposide, and anti-Fas antibody in human T-lymphoma cell line (Jurkat cells)", J. Phannacol. Exp. Then 300, 939–945.
   PubMed Web of Science ®Google Scholar
• Grubb, D.R., Ly, J.D., Vaillant, F., Johnson, K.L. and Lawen, A. (2001) "Mitochondrial cytochrome c release is caspase-dependent and does not involve mitochondrial permeability transition in didemnin B-induced apoptosis", Oncogene 20, 4085–4094.
   PubMed Web of Science ®Google Scholar
• Rapoport, A.P., Simons-Evelyn, M., Chen, T., Side11, R., Luhowskyj, S., Rose11, K., Obrig, T., Hicks, D., Hinkle, P.M., Nahm, M., Insel, R.A. and Abboud, C.N. (2001) "Flavopiridol induces apoptosis and caspase-3 activation of a newly characte-rized Burkitt's lymphoma cell line containing mutant p53 genes", Blood Cells Mol. Disorders 27, 610–624.
   Google Scholar
• Witzig, T.E., Timm, M., Stenson, M., Svingen, P.A. and Kaufmann, S.H. (2000) "Induction of apoptosis in malignant B cells by phenylbutyrate or phenylacetate in combination with chemotherapeutic agents", Clin. Cancer Res. 6, 681–692.
   PubMed Web of Science ®Google Scholar
• Castiglioni, P., Martin-Fontecha, A., Milan, G., Tomajer, V., Magni, F., Michaelsson, J., Rugarli, C., Rosato, A. and Bellone, M. (2002) "Apoptosis-dependent subversion of the T-lymphocyte epitope hierarchy in lymphoma cells", Cancer Res. 62, 1116–1122.
   PubMed Web of Science ®Google Scholar
• Belka, C., Schmid, B., Marini, P., Durand, E., Rudner, J., Fahin, H., Bamberg, M., Schulze-Osthoff, K. and Budach, W. (2001) "Sensitization of resistant lymphoma cells to irradiation-induced apoptosis by the death ligand TRAIL", Oncogene 20, 2190–2196.
   PubMed Web of Science ®Google Scholar
• Wen, J., Ramadevi, N., Nguyen, D., Perkins, C., Worthingogn, E. and Bhalla, K. (2000) "Antileukemic drugs increase death receptor 5 levels and enhance Apo-21L-induced apoptosis of human acute leukemia cells", Blood 96, 3900–3906.
   PubMed Web of Science ®Google Scholar
• Secchiero, P., Gonelli, A., Celeghini, C., Mirandola, P., Guidotti, L., Visani, G., Capitani, S. and Zauli, G. (2001) "Activation of the nitric oxide synthase pathway represents a key component of tumor necrosis factor-related apoptosis-inducing ligand-mediated cytotoxicity on hematologic malignancies", Blood 98, 2220–2228.
   PubMed Web of Science ®Google Scholar
• Guo, F., NimmanapallI, R., Paranawithana, S., Wittman, S., Griffin, D., Bali, P., O'Bryan, E., Fumero, C., Wang, HG. and Bhalla, K. (2002) "Ectopic overexpression of second-mitochon-dria derived acivator of caspases (Smac/DIABLO) and cotreat-ment with N-terminus of Smac/DIABLO peptide potentiates epothilone B-derivate- (BMS 247550) and Apo-2L/TRAIL-induced apoptosis", Blood 99, 3419–3426.
   PubMed Web of Science ®Google Scholar