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Leukemia & Lymphoma Volume 44, 2003 - Issue 2
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Research Article

Flavopiridol Induces Apoptosis in B-cell Chronic Lymphocytic Leukaemia Cells Through a p38 and ERK MAP Kinase-dependent Mechanism

Chris Pepper Department of Haematology, Llandough Hospital, Penlan Road, Penarth, Vale of Glamorgan, CF64 2XX, UK
,
Alun Thomas Department of Haematology, Llandough Hospital, Penlan Road, Penarth, Vale of Glamorgan, CF64 2XX, UK
,
Chris Fegan Department of Haematology, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham, B9 5SS, UK
,
Terry Hoy Department of Haematology, University of Wales College of Medicine, Cardiff, CF4 4XN, UK
&
Paul Bentley Department of Haematology, Llandough Hospital, Penlan Road, Penarth, Vale of Glamorgan, CF64 2XX, UK
Pages 337-342 | Published online: 01 Jul 2009

  • Reed, J.C. (1998) "Molecular biology of chronic lymphocytic leukemia: implications for therapy", Semin. Hermatol. 35, 3-13.
  • O'Brien, S., Giglio, A. and Keating, M.J. (1995) "Advnaces in the biology and treatment of chronic lymphotic leukemia", Blood 85, 307-318.
  • Pepper, C., Hoy, T, and Bentely, D.P. (1997) "Bcl-2/Bax ratios in chronic lymphocytic leukaemia and their correlation with in vitro apoptosis and clinical resistance", Br. J. Cancer 76, 935-938.
  • Robertson, L.E., Plunkett, W., McConnell, K., Keating, M.J. and McDonnell, T.J. (1996) "Bcl-2 expression in chronic lymphocytic leukemia and its correlation with the induction of apoptosis and clinical outcome", Leukemia 10, 456-459.
  • EI Rouby, S., Thomas, A., Costin, D., Rosenberg, C.R., Potesmil, M., Silber, R. and Newcombe, E. (1993) "p53 gene mutation in B-cell chronic lymphocytic leukemia is associated with drug resistance and its independent of MDR1/MDR3 gene expression", Blood 82, 3452-3459.
  • Dohner, H., Fischer, K. Bentz, M., Hansen, K., Benner, A., Cabot, G., Diehl, D., Schlenk, R., Coy, J., Stilgenbauer, S., Volkmann, M., Galle, P.R., Poustka, A., Hunstein, W. and Lichter, P. (1995) "p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell lymphocytic leukemia", Blood 85, 1580-1589.
  • Wattel, E., Preudhomme, C., Hecquet, B., Vanrunbeke, M., Quensnel, B., Dervite, L., Morel, P. and Fenaux, P. (1994) "p53 mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies", Blood 84, 3148-3157.
  • Anastasi, J., Le Beau, M.M., Vardiman, J.W., Fernald, A.A., Larson, R.A. and Rowley, J.D. (1992) "Detection of trisomy 12 in chronic lymphocytic leukemia by fluorescence in situ hybridization to interphase cells: a simple and sensitive method", Blood 79, 1796-1801.
  • Momand, J., Zambetti, G.P., Olson, D.C., George, D. and Levine, A.J. (1992) "The mdm-2 oncogene product forms a complex with the p53 proteins and inhibits p53-mediated transactivation", Cell 69, 1237-1245.
  • Watanabe, T., Hotta, T., Ichikawa, A., Kinoshita, T., Nagai, H., Uchida, T., Murate, T. and Saito, H. (1994) "The MDM2 oncogene overexpression in chronic lymphocytic leukemia and low-grade lymphoma of B-cell origin", Blood 84, 3158-3165.
  • Pepper, C., Bentley, P. and Hoy, T. (1996) "Regulation of clinical chemoresistance by bcl-2 and bax oncoproteins in B-cell chronic lymphocytic leukaemia", Br. J. Haematol. 95, 513-517.
  • Aguilar-Santelises, M., Rottenberg, M.E., Lewin, N., Mellstedt, H. and Jondal, M. (1996) "Bcl-2, bax and p53 expression in B-CLL in relation to in vitro survival and clinical progression", Int. J. Cancer 69, 114-119.
  • Thomas, A., EI Rouby, S., Reed, J.C., Krajewski, S., Silber, R., Potmesil, M. and Newcomb, E.W. (1996) "Drug-induced apoptosis in B-cell chronic lymphocytic leukemia: relationship between P53 gene mutation and bcl-2/bax proteins in drug resistance", Oncogene 12, 1055-1062.
  • Selvakumaran, M., Lin, H-K., Miyashita, T., Wang, H.G., Krajewski, S., Reed, J.C., Hoffman, B. and Libermann, D. (1994) "Immediate early up-regulation of bax expression by p53 but not TGFß1: a paradigm for distinct apoptotic pathways", Oncogene 9, 1791-1798.
  • Caelles, C., Helmberg, A. and Karin, M. (1994) "p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes", Nature 370, 220-223.
  • Hanada, M., Delia, D., Aiello, A., Stadtmauer, E. and Reed, J.C. (1993) "bcl-2 gene hypomethylation and high level expression in B-cell chronic lymphocytic leukemia", Blood 82, 1820-1828.
  • Pepper, C., Thomas, A., Hoy, T. and Bentley, P. (1999) "Chlorambucil resistance in B-cell chronic lymphocytic leukaemia is mediated through failed Bax induction and selection of high Bcl-2-expression subclones", Br. J. Haematol. 104, 581-588.
  • Sedlacek, H.H. (1996) "Mechanisms of action of flavopiridol (review)", Crit. Rev. Oncol. Hematol. 38, 139-170.
  • Kim, K.S., Sack, J.S., Tokarski, J.S., Qian, L., Chao, S.T., Leith, L., Kelly, Y.F., Misra, R.N., Hunt, J.T., Kimball, S.D., Humphreys, W.G., Wautlet, B.S., Mulheron, J.G. and Webster, K.R. (2000) "Thio-and oxyflavopiridols, cyclin-dependent kinase-1 selective inhibitors: synthesis and biological effects", J. Med. Chem. 43, 4126-4134.
  • Byrd, J.C., Shinn, C., Waselenko, J.K., Fuchs, E.J., Lehman, T.A., Nguyen, P.L., Flinn, I.W., Diehl, L.F., Sausville, E. and Grever, M.R. (1998) "Flavopiridol induces apoptosis in chronic lymphocytic leukemia cells via activation of caspase-2 without evidence of bcl-2 modulation or dependence on functional p53", Blood 92, 3804-3816.
  • Pepper, C., Thomas, A., Hoy, T., Fegan, C. and Bentley, P. (2001) "Flavopiridol circumvents Bcl-2 family mediated inhibition of apoptosis and drug resistance in B-cell chronic lymphocytic leukaemia", Br. J. Haematol. 114, 70-77.
  • Binet, J.L., Auquier, A., Dighiero, G., Chastang, C., Piguet, H., Goasguen, J., Vaugier, G., Potron, G., Colona, P., Oberling, F., Thomas, M., Tchernia, G., Jacquillat, C. and Boivin, P. (1981) "A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis", Cancer 48, 198-206.
  • Pepper, C., Thomas, A., Hoy, T., Cotter, F. and Bentley, P. (1999) "Antisense-meidated suppression of Bcl-2 highlights its pivotal role in failed apoptosis in B-cell chronic lymphocytic leukaemia", Br. J. Haematol. 107, 611-615.
  • Ferlini, C., Di Cesare, S., Rainaldi, G., Malorni, W., Samoggia, P., Biselli, R. and Fattorossi, A. (1996) "Flow cytometric analysis of the early phase of apoptosis by cellular and nuclear techniques", Cytometry 24, 106-115.
  • Vermes, L., Haanen, C., Steffens-Nakken, H. and Reutelingsperger, C. (1995) "A novel essay for apoptosis: flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V", J. Immunol. Methods 184, 39-51.
  • Galcheva-Gargova, Z., Derijard, B., Wu, I.H. and Davis, R.J. (1994) "An osmosensing signal transduction pathway in mammalian cells", Science 265, 806-808.
  • Xia, Z., Dichens, M., Raingeaud, J., Davis, R.J. and Greenberg, M.E. (1995) "Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis", Science 270, 1326-1331.
  • Zhang, Y., Huang, Y., Rishi, A.K., Sheikh, M.S., Shroot, B., Reichert, U., Dawson, M., Poirer, G. and Fontana, J.A. (1999) "Activation of the p38 and JNK/SAPK mitogen-activated protein kinase pathways during apoptosis is mediated by novel retinoid", Exp. Cell Res. 247, 233-240.
  • Nick, J.A., Avdi, N.J., Gerwins, P., Johnson, G.L. and Worten, G.S. (1996) "Activation of p38 mitogen-activated protein kinase in human neutrophils by lipopolysaccharide", J. Immunol. 156, 4867-4875.
  • Anderson, S.M., Reyland, M.E., Hunter, S., Diesher, L.M., Barzen, K.A. and Quissell, D.O. (1999) "Etoposide-induced activation of c-jun N-terminal kinase (JNK) correlates with drug induced apoptosis in salivary gland acinar cells", Cell Death Differ. 6, 454-462.
  • Stadheim, T.A. and Kucera, G.L. (1998) "Extracellular signal-regulated kinase (ERK) activity is required for TPA-mediated inhibition of drug-induced apoptosis", Biochem. Biophys. Res. Commun. 245, 266-271.
  • Barragan, M., Bellosillo, B., Campas, C., Colomer, D., Pons, G. and Gil, J. (2002) "Involvement of protein kinase C and phosphatidylinositol 3-kinase pathways in the survival of B-cell chronic lymphocytic leukemia cells", Blood 99, 2969-2976.

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