Blockade of the Bcr-Abl Kinase Activity Induces Apoptosis of Chronic Myelogenous Leukemia Cells by Suppressing Signal Transducer and Activator of Transcription 5-Dependent Expression of Bcl-XL

doi:10.1084/jem.191.6.977

Published online 20 March 2000.

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© The Rockefeller University Press, 0022-1007/2000/3/977/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 6, March 20, 2000 977-984

Original Article

Blockade of the Bcr-Abl Kinase Activity Induces Apoptosis of Chronic Myelogenous Leukemia Cells by Suppressing Signal Transducer and Activator of Transcription 5–Dependent Expression of Bcl-X_L

Machiko Horita^a, Enrique Jose Andreu^b, Adalberto Benito^a, Cristina Arbona^b, Cristina Sanz^a, Isana Benet^b, Felipe Prosper^b, and Jose Luis Fernandez-Luna^a

^a Seccion de Inmunologia, Hospital Universitario Marques de Valdecilla, Instituto Nacional de la Salud, 39008 Santander, Spain
^b Departamento de Hematologia y Oncologia Medica, Hospital Clinico Universitario, 46010 Valencia, Spain
Seccion de Inmunologia, Hospital Universitario Marques de Valdecilla, INSALUD, 39008 Santander, Spain.34-942-20345334-942-203453

inmflj{at}humv.es

Bcr-Abl–expressing leukemic cells are highly resistantto apoptosis induced by chemotherapeutic drugs. Although a numberof signaling molecules have been shown to be activated by theBcr-Abl kinase, the antiapoptotic pathway triggered by thisoncogene has not been elucidated. Here, we show that the interleukin3-independent expression of the antiapoptotic protein, Bcl-x_L,is induced by Bcr-Abl through activation of signal transducerand activator of transcription (Stat)5. Inhibition of the Bcr-Ablkinase activity in Bcr-Abl–expressing cell lines and CD34⁺cells from chronic myelogenous leukemia (CML) patients inducesapoptosis by suppressing the capacity of Stat5 to interact withthe bcl-x promoter. Interestingly, after inhibition of the Bcr-Ablkinase, the expression of Bcl-x_L is downregulated more rapidlyin chronic phase than in blast crisis CML cells, suggestingan involvement of this protein in disease progression. Overall,we describe a novel antiapoptotic pathway triggered by Bcr-Ablthat may contribute to the resistance of CML cells to undergoapoptosis.

Key Words: CGP 57148 • cell death • blast crisis • promoter • interleukin 3

M. Horita and E.J. Andreu contributed equally to this work.

A. Benito's present address is Department of Pathology, Universityof Michigan Medical School, 1500 E. Medical Center Dr., AnnArbor, MI 48109.

Abbreviations used in this paper: CML, chronic myelogenous leukemia;EMSA, electrophoretic mobility shift assay; IL, interleukin;Stat, signal transducer and activator of transcription.

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Chen, J.-L., Limnander, A., Rothman, P. B. (2008). Pim-1 and Pim-2 kinases are required for efficient pre-B-cell transformation by v-Abl oncogene. Blood 111: 1677-1685 [Abstract] [Full Text]
Jamieson, C. H. (2008). Chronic Myeloid Leukemia Stem Cells. ASH Education Book 2008: 436-442 [Abstract] [Full Text]
Kuo, Y.-Y., Chang, Z.-F. (2007). GATA-1 and Gfi-1B Interplay To Regulate Bcl-xL Transcription. Mol. Cell. Biol. 27: 4261-4272 [Abstract] [Full Text]
Nam, S., Williams, A., Vultur, A., List, A., Bhalla, K., Smith, D., Lee, F. Y., Jove, R. (2007). Dasatinib (BMS-354825) inhibits Stat5 signaling associated with apoptosis in chronic myelogenous leukemia cells. Molecular Cancer Therapeutics 6: 1400-1405 [Abstract] [Full Text]
Wang, Y., Cai, D., Brendel, C., Barett, C., Erben, P., Manley, P. W., Hochhaus, A., Neubauer, A., Burchert, A. (2007). Adaptive secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates imatinib and nilotinib resistance in BCR/ABL+ progenitors via JAK-2/STAT-5 pathway activation. Blood 109: 2147-2155 [Abstract] [Full Text]
Yoon, P., Giafis, N., Smith, J., Mears, H., Katsoulidis, E., Sassano, A., Altman, J., Redig, A. J., Tallman, M. S., Platanias, L. C. (2006). Activation of mammalian target of rapamycin and the p70 S6 kinase by arsenic trioxide in BCR-ABL-expressing cells.. Molecular Cancer Therapeutics 5: 2815-2823 [Abstract] [Full Text]
Nagy, Z. S., Rui, H., Stepkowski, S. M., Karras, J., Kirken, R. A. (2006). A Preferential Role for STAT5, not Constitutively Active STAT3, in Promoting Survival of a Human Lymphoid Tumor. J. Immunol. 177: 5032-5040 [Abstract] [Full Text]
Kuroda, J., Puthalakath, H., Cragg, M. S., Kelly, P. N., Bouillet, P., Huang, D. C. S., Kimura, S., Ottmann, O. G., Druker, B. J., Villunger, A., Roberts, A. W., Strasser, A. (2006). Bim and Bad mediate imatinib-induced killing of Bcr/Abl+ leukemic cells, and resistance due to their loss is overcome by a BH3 mimetic. Proc. Natl. Acad. Sci. USA 103: 14907-14912 [Abstract] [Full Text]
Kaufmann, S. H. (2006). Imatinib spells BAD news for Bcr/abl-positive leukemias. Proc. Natl. Acad. Sci. USA 103: 14651-14652 [Full Text]
Nelson, E. A., Walker, S. R., Li, W., Liu, X. S., Frank, D. A. (2006). Identification of Human STAT5-dependent Gene Regulatory Elements Based on Interspecies Homology. J. Biol. Chem. 281: 26216-26224 [Abstract] [Full Text]
Ye, D., Wolff, N., Li, L., Zhang, S., Ilaria, R. L. Jr (2006). STAT5 signaling is required for the efficient induction and maintenance of CML in mice. Blood 107: 4917-4925 [Abstract] [Full Text]
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Dai, Y., Rahmani, M., Corey, S. J., Dent, P., Grant, S. (2004). A Bcr/Abl-independent, Lyn-dependent Form of Imatinib Mesylate (STI-571) Resistance Is Associated with Altered Expression of Bcl-2. J. Biol. Chem. 279: 34227-34239 [Abstract] [Full Text]
Dai, Y., Rahmani, M., Pei, X.-Y., Dent, P., Grant, S. (2004). Bortezomib and flavopiridol interact synergistically to induce apoptosis in chronic myeloid leukemia cells resistant to imatinib mesylate through both Bcr/Abl-dependent and -independent mechanisms. Blood 104: 509-518 [Abstract] [Full Text]
Calabretta, B., Perrotti, D. (2004). The biology of CML blast crisis. Blood 103: 4010-4022 [Abstract] [Full Text]
Coluccia, A. M. L., Perego, S., Cleris, L., Gunby, R. H., Passoni, L., Marchesi, E., Formelli, F., Gambacorti-Passerini, C. (2004). Bcl-XL down-regulation suppresses the tumorigenic potential of NPM/ALK in vitro and in vivo. Blood 103: 2787-2794 [Abstract] [Full Text]
Gonzalez, I., Andreu, E. J., Panizo, A., Inoges, S., Fontalba, A., Fernandez-Luna, J. L., Gaboli, M., Sierrasesumaga, L., Martin-Algarra, S., Pardo, J., Prosper, F., de Alava, E. (2004). Imatinib Inhibits Proliferation of Ewing Tumor Cells Mediated by the Stem Cell Factor/KIT Receptor Pathway, and Sensitizes Cells to Vincristine and Doxorubicin-Induced Apoptosis. Clin. Cancer Res. 10: 751-761 [Abstract] [Full Text]
Bartolovic, K., Balabanov, S., Hartmann, U., Komor, M., Boehmler, A. M., Buhring, H.-J., Mohle, R., Hoelzer, D., Kanz, L., Hofmann, W.-K., Brummendorf, T. H. (2004). Inhibitory effect of imatinib on normal progenitor cells in vitro. Blood 103: 523-529 [Abstract] [Full Text]
Ferrao, P. T., Frost, M. J., Siah, S.-P., Ashman, L. K. (2003). Overexpression of P-glycoprotein in K562 cells does not confer resistance to the growth inhibitory effects of imatinib (STI571) in vitro. Blood 102: 4499-4503 [Abstract] [Full Text]
Mohapatra, S., Chu, B., Wei, S., Djeu, J., Epling-Burnette, P. K., Loughran, T., Jove, R., Pledger, W. J. (2003). Roscovitine Inhibits STAT5 Activity and Induces Apoptosis in the Human Leukemia Virus Type 1-Transformed Cell Line MT-2. Cancer Res. 63: 8523-8530 [Abstract] [Full Text]
Vlahovic, G., Crawford, J. (2003). Activation of Tyrosine Kinases in Cancer. The Oncologist 8: 531-538 [Abstract] [Full Text]
Minami, Y., Yamamoto, K., Kiyoi, H., Ueda, R., Saito, H., Naoe, T. (2003). Different antiapoptotic pathways between wild-type and mutated FLT3: insights into therapeutic targets in leukemia. Blood 102: 2969-2975 [Abstract] [Full Text]
Wohlbold, L., van der Kuip, H., Miething, C., Vornlocher, H.-P., Knabbe, C., Duyster, J., Aulitzky, W. E. (2003). Inhibition of bcr-abl gene expression by small interfering RNA sensitizes for imatinib mesylate (STI571). Blood 102: 2236-2239 [Abstract] [Full Text]
Faderl, S., Harris, D., Van, Q., Kantarjian, H. M., Talpaz, M., Estrov, Z. (2003). Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces antiapoptotic and proapoptotic signals in acute myeloid leukemia. Blood 102: 630-637 [Abstract] [Full Text]
Wong, S., McLaughlin, J., Cheng, D., Witte, O. N. (2003). Cell context-specific effects of the BCR-ABL oncogene monitored in hematopoietic progenitors. Blood 101: 4088-4097 [Abstract] [Full Text]
Benekli, M., Baer, M. R., Baumann, H., Wetzler, M. (2003). Signal transducer and activator of transcription proteins in leukemias. Blood 101: 2940-2954 [Abstract] [Full Text]
Hietakangas, V., Poukkula, M., Heiskanen, K. M., Karvinen, J. T., Sistonen, L., Eriksson, J. E. (2003). Erythroid Differentiation Sensitizes K562 Leukemia Cells to TRAIL-Induced Apoptosis by Downregulation of c-FLIP. Mol. Cell. Biol. 23: 1278-1291 [Abstract] [Full Text]
Donato, N. J., Wu, J. Y., Stapley, J., Gallick, G., Lin, H., Arlinghaus, R., Talpaz, M. (2003). BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571. Blood 101: 690-698 [Abstract] [Full Text]
Jiang, X., Ng, E., Yip, C., Eisterer, W., Chalandon, Y., Stuible, M., Eaves, A., Eaves, C. J. (2002). Primitive interleukin 3 null hematopoietic cells transduced with BCR-ABL show accelerated loss after culture of factor-independence in vitro and leukemogenic activity in vivo. Blood 100: 3731-3740 [Abstract] [Full Text]
Mayerhofer, M., Valent, P., Sperr, W. R., Griffin, J. D., Sillaber, C. (2002). BCR/ABL induces expression of vascular endothelial growth factor and its transcriptional activator, hypoxia inducible factor-1alpha , through a pathway involving phosphoinositide 3-kinase and the mammalian target of rapamycin. Blood 100: 3767-3775 [Abstract] [Full Text]
Kazi, A., Smith, D. M., Zhong, Q., Dou, Q. P. (2002). Inhibition of Bcl-XL Phosphorylation by Tea Polyphenols or Epigallocatechin-3-Gallate Is Associated with Prostate Cancer Cell Apoptosis. Mol. Pharmacol. 62: 765-771 [Abstract] [Full Text]
Hinz, M., Lemke, P., Anagnostopoulos, I., Hacker, C., Krappmann, D., Mathas, S., Dorken, B., Zenke, M., Stein, H., Scheidereit, C. (2002). Nuclear Factor {kappa}B-dependent Gene Expression Profiling of Hodgkin's Disease Tumor Cells, Pathogenetic Significance, and Link to Constitutive Signal Transducer and Activator of Transcription 5a Activity. JEM 196: 605-617 [Abstract] [Full Text]
Slupianek, A., Hoser, G., Majsterek, I., Bronisz, A., Malecki, M., Blasiak, J., Fishel, R., Skorski, T. (2002). Fusion Tyrosine Kinases Induce Drug Resistance by Stimulation of Homology-Dependent Recombination Repair, Prolongation of G2/M Phase, and Protection from Apoptosis. Mol. Cell. Biol. 22: 4189-4201 [Abstract] [Full Text]
Nieborowska-Skorska, M., Hoser, G., Kossev, P., Wasik, M. A., Skorski, T. (2002). Complementary functions of the antiapoptotic protein A1 and serine/threonine kinase pim-1 in the BCR/ABL-mediated leukemogenesis. Blood 99: 4531-4539 [Abstract] [Full Text]
Holtz, M. S., Slovak, M. L., Zhang, F., Sawyers, C. L., Forman, S. J., Bhatia, R. (2002). Imatinib mesylate (STI571) inhibits growth of primitive malignant progenitors in chronic myelogenous leukemia through reversal of abnormally increased proliferation. Blood 99: 3792-3800 [Abstract] [Full Text]
Iervolino, A., Santilli, G., Trotta, R., Guerzoni, C., Cesi, V., Bergamaschi, A., Gambacorti-Passerini, C., Calabretta, B., Perrotti, D. (2002). hnRNP A1 Nucleocytoplasmic Shuttling Activity Is Required for Normal Myelopoiesis and BCR/ABL Leukemogenesis. Mol. Cell. Biol. 22: 2255-2266 [Abstract] [Full Text]
Baron, F., Turhan, A. G., Giron-Michel, J., Azzarone, B., Bentires-Alj, M., Bours, V., Bourhis, J. H., Chouaib, S., Caignard, A. (2002). Leukemic target susceptibility to natural killer cytotoxicity: relationship with BCR-ABL expression. Blood 99: 2107-2113 [Abstract] [Full Text]
Sonoyama, J., Matsumura, I., Ezoe, S., Satoh, Y., Zhang, X., Kataoka, Y., Takai, E., Mizuki, M., Machii, T., Wakao, H., Kanakura, Y. (2002). Functional Cooperation among Ras, STAT5, and Phosphatidylinositol 3-Kinase Is Required for Full Oncogenic Activities of BCR/ABL in K562 Cells. J. Biol. Chem. 277: 8076-8082 [Abstract] [Full Text]
Dorsey, J. F., Cunnick, J. M., Mane, S. M., Wu, J. (2002). Regulation of the Erk2-Elk1 signaling pathway and megakaryocytic differentiation of Bcr-Abl+ K562 leukemic cells by Gab2. Blood 99: 1388-1397 [Abstract] [Full Text]
Mow, B. M. F., Chandra, J., Svingen, P. A., Hallgren, C. G., Weisberg, E., Kottke, T. J., Narayanan, V. L., Litzow, M. R., Griffin, J. D., Sausville, E. A., Tefferi, A., Kaufmann, S. H. (2002). Effects of the Bcr/abl kinase inhibitors STI571 and adaphostin (NSC 680410) on chronic myelogenous leukemia cells in vitro. Blood 99: 664-671 [Abstract] [Full Text]
Yu, C., Krystal, G., Varticovksi, L., McKinstry, R., Rahmani, M., Dent, P., Grant, S. (2002). Pharmacologic Mitogen-activated Protein/Extracellular Signal-regulated Kinase Kinase/Mitogen-activated Protein Kinase Inhibitors Interact Synergistically with STI571 to Induce Apoptosis in Bcr/Abl-expressing Human Leukemia Cells. Cancer Res. 62: 188-199 [Abstract] [Full Text]
Ghaffari, S., Kitidis, C., Fleming, M. D., Neubauer, H., Pfeffer, K., Lodish, H. F. (2001). Erythropoiesis in the absence of janus-kinase 2: BCR-ABL induces red cell formation in JAK2-/- hematopoietic progenitors. Blood 98: 2948-2957 [Abstract] [Full Text]
Wolff, N. C., Ilaria, R. L. Jr (2001). Establishment of a murine model for therapy-treated chronic myelogenous leukemia using the tyrosine kinase inhibitor STI571. Blood 98: 2808-2816 [Abstract] [Full Text]
Goetz, A. W., van der Kuip, H., Maya, R., Oren, M., Aulitzky, W. E. (2001). Requirement for Mdm2 in the Survival Effects of Bcr-Abl and Interleukin 3 in Hematopoietic Cells. Cancer Res. 61: 7635-7641 [Abstract] [Full Text]
van der Kuip, H., Goetz, A. W., Miething, C., Duyster, J., Aulitzky, W. E. (2001). Adhesion to fibronectin selectively protects Bcr-Abl+ cells from DNA damage-induced apoptosis. Blood 98: 1532-1541 [Abstract] [Full Text]
Cetkovic-Cvrlje, M., Roers, B. A., Waurzyniak, B., Liu, X.-P., Uckun, F. M. (2001). Targeting Janus kinase 3 to attenuate the severity of acute graft-versus-host disease across the major histocompatibility barrier in mice. Blood 98: 1607-1613 [Abstract] [Full Text]
Di Pietro, R., Secchiero, P., Rana, R., Gibellini, D., Visani, G., Bemis, K., Zamai, L., Miscia, S., Zauli, G. (2001). Ionizing radiation sensitizes erythroleukemic cells but not normal erythroblasts to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated cytotoxicity by selective up-regulation of TRAIL-R1. Blood 97: 2596-2603 [Abstract] [Full Text]
Donato, N. J., Wu, J. Y., Zhang, L., Kantarjian, H., Talpaz, M. (2001). Down-regulation of interleukin-3/granulocyte-macrophage colony-stimulating factor receptor {beta}-chain in BCR-ABL+ human leukemic cells: association with loss of cytokine-mediated Stat-5 activation and protection from apoptosis after BCR-ABL inhibition. Blood 97: 2846-2853 [Abstract] [Full Text]
Chen, H., Lee, J. M., Zong, Y., Borowitz, M., Ng, M. H., Ambinder, R. F., Hayward, S. D. (2001). Linkage between STAT Regulation and Epstein-Barr Virus Gene Expression in Tumors. J. Virol. 75: 2929-2937 [Abstract] [Full Text]
Hasinoff, B. B., Abram, M. E., Barnabé, N., Khélifa, T., Allan, W. P., Yalowich, J. C. (2001). The Catalytic DNA Topoisomerase II Inhibitor Dexrazoxane (ICRF-187) Induces Differentiation and Apoptosis in Human Leukemia K562 Cells. Mol. Pharmacol. 59: 453-461 [Abstract] [Full Text]
Deininger, M. W. N., Goldman, J. M., Melo, J. V. (2000). The molecular biology of chronic myeloid leukemia. Blood 96: 3343-3356 [Full Text]
Gambacorti-Passerini, C., Barni, R., le Coutre, P., Zucchetti, M., Cabrita, G., Cleris, L., Rossi, F., Gianazza, E., Brueggen, J., Cozens, R., Pioltelli, P., Pogliani, E., Corneo, G., Formelli, F., D'Incalci, M. (2000). Role of {alpha}1 Acid Glycoprotein in the In Vivo Resistance of Human BCR-ABL+ Leukemic Cells to the Abl Inhibitor STI571. JNCI J Natl Cancer Inst 92: 1641-1650 [Abstract] [Full Text]
Gesbert, F., Griffin, J. D. (2000). Bcr/Abl activates transcription of the Bcl-X gene through STAT5. Blood 96: 2269-2276 [Abstract] [Full Text]
Ehret, G. B., Reichenbach, P., Schindler, U., Horvath, C. M., Fritz, S., Nabholz, M., Bucher, P. (2001). DNA Binding Specificity of Different STAT Proteins. COMPARISON OF IN VITRO SPECIFICITY WITH NATURAL TARGET SITES. J. Biol. Chem. 276: 6675-6688 [Abstract] [Full Text]
Masuda, A., Matsuguchi, T., Yamaki, K., Hayakawa, T., Yoshikai, Y. (2001). Interleukin-15 Prevents Mouse Mast Cell Apoptosis through STAT6-mediated Bcl-xL Expression. J. Biol. Chem. 276: 26107-26113 [Abstract] [Full Text]