Literature DB >> 16997913

Bim and Bad mediate imatinib-induced killing of Bcr/Abl+ leukemic cells, and resistance due to their loss is overcome by a BH3 mimetic.

Junya Kuroda1, Hamsa Puthalakath, Mark S Cragg, Priscilla N Kelly, Philippe Bouillet, David C S Huang, Shinya Kimura, Oliver G Ottmann, Brian J Druker, Andreas Villunger, Andrew W Roberts, Andreas Strasser.   

Abstract

Cell killing is a critical pharmacological activity of imatinib to eradicate Bcr/Abl+ leukemias. We found that imatinib kills Bcr/Abl+ leukemic cells by triggering the Bcl-2-regulated apoptotic pathway. Imatinib activated several proapoptotic BH3-only proteins: bim and bmf transcription was increased, and both Bim and Bad were activated posttranslationally. Studies using RNAi and cells from gene-targeted mice revealed that Bim plays a major role in imatinib-induced apoptosis of Bcr/Abl+ leukemic cells and that the combined loss of Bim and Bad abrogates this killing. Loss of Bmf or Puma had no effect. Resistance to imatinib caused by Bcl-2 overexpression or loss of Bim (plus Bad) could be overcome by cotreatment with the BH3 mimetic ABT-737. These results demonstrate that Bim and Bad account for most, perhaps all, imatinib-induced killing of Bcr/Abl+ leukemic cells and suggest previously undescribed drug combination strategies for cancer therapy.

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Year:  2006        PMID： 16997913      PMCID： PMC1595449          DOI： 10.1073/pnas.0606176103

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN： 0027-8424            Impact factor:   11.205


  26 in total

1.  Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity.

Authors:  P Bouillet; D Metcalf; D C Huang; D M Tarlinton; T W Kay; F Köntgen; J M Adams; A Strasser
Journal:  Science       Date:  1999-11-26       Impact factor: 47.728

Review 2.  BH3-Only proteins-essential initiators of apoptotic cell death.

Authors:  D C Huang; A Strasser
Journal:  Cell       Date:  2000-12-08       Impact factor: 41.582

3.  Activation of Fas by FasL induces apoptosis by a mechanism that cannot be blocked by Bcl-2 or Bcl-x(L).

Authors:  D C Huang; M Hahne; M Schroeter; K Frei; A Fontana; A Villunger; K Newton; J Tschopp; A Strasser
Journal:  Proc Natl Acad Sci U S A       Date:  1999-12-21       Impact factor: 11.205

4.  Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis.

Authors:  H Puthalakath; A Villunger; L A O'Reilly; J G Beaumont; L Coultas; R E Cheney; D C Huang; A Strasser
Journal:  Science       Date:  2001-09-07       Impact factor: 47.728

Review 5.  Apoptosis signaling.

Authors:  A Strasser; L O'Connor; V M Dixit
Journal:  Annu Rev Biochem       Date:  2000       Impact factor: 23.643

6.  Bad-deficient mice develop diffuse large B cell lymphoma.

Authors:  Ann M Ranger; Jiping Zha; Hisashi Harada; Sandeep Robert Datta; Nika N Danial; Andrew P Gilmore; Jeffery L Kutok; Michelle M Le Beau; Michael E Greenberg; Stanley J Korsmeyer
Journal:  Proc Natl Acad Sci U S A       Date:  2003-07-22       Impact factor: 11.205

7.  Constitutive Bcl-2 expression throughout the hematopoietic compartment affects multiple lineages and enhances progenitor cell survival.

Authors:  S Ogilvy; D Metcalf; C G Print; M L Bath; A W Harris; J M Adams
Journal:  Proc Natl Acad Sci U S A       Date:  1999-12-21       Impact factor: 11.205

8.  An inhibitor of Bcl-2 family proteins induces regression of solid tumours.

Authors:  Tilman Oltersdorf; Steven W Elmore; Alexander R Shoemaker; Robert C Armstrong; David J Augeri; Barbara A Belli; Milan Bruncko; Thomas L Deckwerth; Jurgen Dinges; Philip J Hajduk; Mary K Joseph; Shinichi Kitada; Stanley J Korsmeyer; Aaron R Kunzer; Anthony Letai; Chi Li; Michael J Mitten; David G Nettesheim; ShiChung Ng; Paul M Nimmer; Jacqueline M O'Connor; Anatol Oleksijew; Andrew M Petros; John C Reed; Wang Shen; Stephen K Tahir; Craig B Thompson; Kevin J Tomaselli; Baole Wang; Michael D Wendt; Haichao Zhang; Stephen W Fesik; Saul H Rosenberg
Journal:  Nature       Date:  2005-05-15       Impact factor: 49.962

Review 9.  Keeping killers on a tight leash: transcriptional and post-translational control of the pro-apoptotic activity of BH3-only proteins.

Authors:  H Puthalakath; A Strasser
Journal:  Cell Death Differ       Date:  2002-05       Impact factor: 15.828

10.  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.

Authors:  M Horita; E J Andreu; A Benito; C Arbona; C Sanz; I Benet; F Prosper; J L Fernandez-Luna
Journal:  J Exp Med       Date:  2000-03-20       Impact factor: 14.307
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  143 in total

1.  Alternative splicing of Bim and Erk-mediated Bim(EL) phosphorylation are dispensable for hematopoietic homeostasis in vivo.

Authors:  C Clybouw; D Merino; T Nebl; F Masson; M Robati; L O'Reilly; A Hübner; R J Davis; A Strasser; P Bouillet
Journal:  Cell Death Differ       Date:  2012-01-13       Impact factor: 15.828

Review 2.  BH3-only proteins in apoptosis at a glance.

Authors:  Lina Happo; Andreas Strasser; Suzanne Cory
Journal:  J Cell Sci       Date:  2012-03-01       Impact factor: 5.285

3.  Cyclic-AMP-dependent protein kinase A regulates apoptosis by stabilizing the BH3-only protein Bim.

Authors:  Diane Moujalled; Ross Weston; Holly Anderton; Robert Ninnis; Pranay Goel; Andrew Coley; David C S Huang; Li Wu; Andreas Strasser; Hamsa Puthalakath
Journal:  EMBO Rep       Date:  2010-12-10       Impact factor: 8.807

4.  Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers.

Authors:  Ryohei Katayama; Alice T Shaw; Tahsin M Khan; Mari Mino-Kenudson; Benjamin J Solomon; Balazs Halmos; Nicholas A Jessop; John C Wain; Alan Tien Yeo; Cyril Benes; Lisa Drew; Jamal Carlos Saeh; Katherine Crosby; Lecia V Sequist; A John Iafrate; Jeffrey A Engelman
Journal:  Sci Transl Med       Date:  2012-01-25       Impact factor: 17.956

5.  Imatinib spells BAD news for Bcr/abl-positive leukemias.

Authors:  Scott H Kaufmann
Journal:  Proc Natl Acad Sci U S A       Date:  2006-09-26       Impact factor: 11.205

Review 6.  The Bcl-2 apoptotic switch in cancer development and therapy.

Authors:  J M Adams; S Cory
Journal:  Oncogene       Date:  2007-02-26       Impact factor: 9.867

7.  Aerobic glycolysis suppresses p53 activity to provide selective protection from apoptosis upon loss of growth signals or inhibition of BCR-Abl.

Authors:  Emily F Mason; Yuxing Zhao; Pankuri Goraksha-Hicks; Jonathan L Coloff; Hugh Gannon; Stephen N Jones; Jeffrey C Rathmell
Journal:  Cancer Res       Date:  2010-09-28       Impact factor: 12.701

8.  Proapoptotic BH3-only protein Bim is essential for developmentally programmed death of germinal center-derived memory B cells and antibody-forming cells.

Authors:  Silke F Fischer; Philippe Bouillet; Kristy O'Donnell; Amanda Light; David M Tarlinton; Andreas Strasser
Journal:  Blood       Date:  2007-08-24       Impact factor: 22.113

Review 9.  Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy.

Authors:  Peter E Czabotar; Guillaume Lessene; Andreas Strasser; Jerry M Adams
Journal:  Nat Rev Mol Cell Biol       Date:  2014-01       Impact factor: 94.444

10.  Therapeutic efficacy of ABT-737, a selective inhibitor of BCL-2, in small cell lung cancer.

Authors:  Christine L Hann; Vincent C Daniel; Elizabeth A Sugar; Irina Dobromilskaya; Sara C Murphy; Leslie Cope; Xue Lin; Jared S Hierman; Daniel L Wilburn; D Neil Watkins; Charles M Rudin
Journal:  Cancer Res       Date:  2008-04-01       Impact factor: 12.701
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