@article{RN6200,
   author = {Steidl, U. and Rosenbauer, F. and Verhaak, R. G. and Gu, X. and Ebralidze, A. and Otu, H. H. and Klippel, S. and Steidl, C. and Bruns, I. and Costa, D. B. and Wagner, K. and Aivado, M. and Kobbe, G. and Valk, P. J. and Passegué, E. and Libermann, T. A. and Delwel, R. and Tenen, D. G.},
   title = {Essential role of Jun family transcription factors in PU.1 knockdown-induced leukemic stem cells},
   journal = {Nat Genet},
   volume = {38},
   number = {11},
   pages = {1269-77},
   note = {Steidl, Ulrich
Rosenbauer, Frank
Verhaak, Roel G W
Gu, Xuesong
Ebralidze, Alexander
Otu, Hasan H
Klippel, Steffen
Steidl, Christian
Bruns, Ingmar
Costa, Daniel B
Wagner, Katharina
Aivado, Manuel
Kobbe, Guido
Valk, Peter J M
Passegué, Emmanuelle
Libermann, Towia A
Delwel, Ruud
Tenen, Daniel G
CA41456/CA/NCI NIH HHS/United States
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
United States
2006/10/17
Nat Genet. 2006 Nov;38(11):1269-77. doi: 10.1038/ng1898. Epub 2006 Oct 15.},
   abstract = {Knockdown of the transcription factor PU.1 (encoded by Sfpi1) leads to acute myeloid leukemia (AML) in mice. We examined the transcriptome of preleukemic hematopoietic stem cells (HSCs) in which PU.1 was knocked down (referred to as 'PU.1-knockdown HSCs') to identify transcriptional changes preceding malignant transformation. Transcription factors c-Jun and JunB were among the top-downregulated targets. Restoration of c-Jun expression in preleukemic cells rescued the PU.1 knockdown-initiated myelomonocytic differentiation block. Lentiviral restoration of JunB at the leukemic stage led to loss of leukemic self-renewal capacity and prevented leukemia in NOD-SCID mice into which leukemic PU.1-knockdown cells were transplanted. Examination of human individuals with AML confirmed the correlation between PU.1 and JunB downregulation. These results delineate a transcriptional pattern that precedes leukemic transformation in PU.1-knockdown HSCs and demonstrate that decreased levels of c-Jun and JunB contribute to the development of PU.1 knockdown-induced AML by blocking differentiation and increasing self-renewal. Therefore, examination of disturbed gene expression in HSCs can identify genes whose dysregulation is essential for leukemic stem cell function and that are targets for therapeutic interventions.},
   keywords = {Animals
Cell Differentiation/genetics
Cell Transformation, Neoplastic/genetics
Down-Regulation
Granulocytes/cytology
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells/cytology/metabolism/*pathology
Humans
Leukemia, Myeloid, Acute/*genetics/metabolism/pathology
Mice
Mice, Inbred NOD
Mice, Knockout
Mice, SCID
Monocytes/cytology
Proto-Oncogene Proteins/*genetics/metabolism
Proto-Oncogene Proteins c-jun/genetics/metabolism/*physiology
Trans-Activators/*genetics/metabolism
Transcription, Genetic
Transduction, Genetic},
   ISSN = {1061-4036 (Print)
1061-4036},
   DOI = {10.1038/ng1898},
   year = {2006},
   type = {Journal Article}
}

{"_id":"3m56KxjRo8CJePWrN","bibbaseid":"steidl-rosenbauer-verhaak-gu-ebralidze-otu-klippel-steidl-etal-essentialroleofjunfamilytranscriptionfactorsinpu1knockdowninducedleukemicstemcells-2006","authorIDs":["5dce3b23dcea22df0100007c","5dec52fce16431f2010000c9","5dec5944e16431f2010000fa","5e0a5e7ace3ebce40100010e","5e2ff5be5bfc8ede0100003b","c8zrScQz6casKGL4t"],"author_short":["Steidl, U.","Rosenbauer, F.","Verhaak, R. G.","Gu, X.","Ebralidze, A.","Otu, H. H.","Klippel, S.","Steidl, C.","Bruns, I.","Costa, D. B.","Wagner, K.","Aivado, M.","Kobbe, G.","Valk, P. J.","Passegué, E.","Libermann, T. A.","Delwel, R.","Tenen, D. G."],"bibdata":{"bibtype":"article","type":"Journal Article","author":[{"propositions":[],"lastnames":["Steidl"],"firstnames":["U."],"suffixes":[]},{"propositions":[],"lastnames":["Rosenbauer"],"firstnames":["F."],"suffixes":[]},{"propositions":[],"lastnames":["Verhaak"],"firstnames":["R.","G."],"suffixes":[]},{"propositions":[],"lastnames":["Gu"],"firstnames":["X."],"suffixes":[]},{"propositions":[],"lastnames":["Ebralidze"],"firstnames":["A."],"suffixes":[]},{"propositions":[],"lastnames":["Otu"],"firstnames":["H.","H."],"suffixes":[]},{"propositions":[],"lastnames":["Klippel"],"firstnames":["S."],"suffixes":[]},{"propositions":[],"lastnames":["Steidl"],"firstnames":["C."],"suffixes":[]},{"propositions":[],"lastnames":["Bruns"],"firstnames":["I."],"suffixes":[]},{"propositions":[],"lastnames":["Costa"],"firstnames":["D.","B."],"suffixes":[]},{"propositions":[],"lastnames":["Wagner"],"firstnames":["K."],"suffixes":[]},{"propositions":[],"lastnames":["Aivado"],"firstnames":["M."],"suffixes":[]},{"propositions":[],"lastnames":["Kobbe"],"firstnames":["G."],"suffixes":[]},{"propositions":[],"lastnames":["Valk"],"firstnames":["P.","J."],"suffixes":[]},{"propositions":[],"lastnames":["Passegué"],"firstnames":["E."],"suffixes":[]},{"propositions":[],"lastnames":["Libermann"],"firstnames":["T.","A."],"suffixes":[]},{"propositions":[],"lastnames":["Delwel"],"firstnames":["R."],"suffixes":[]},{"propositions":[],"lastnames":["Tenen"],"firstnames":["D.","G."],"suffixes":[]}],"title":"Essential role of Jun family transcription factors in PU.1 knockdown-induced leukemic stem cells","journal":"Nat Genet","volume":"38","number":"11","pages":"1269-77","note":"Steidl, Ulrich Rosenbauer, Frank Verhaak, Roel G W Gu, Xuesong Ebralidze, Alexander Otu, Hasan H Klippel, Steffen Steidl, Christian Bruns, Ingmar Costa, Daniel B Wagner, Katharina Aivado, Manuel Kobbe, Guido Valk, Peter J M Passegué, Emmanuelle Libermann, Towia A Delwel, Ruud Tenen, Daniel G CA41456/CA/NCI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States 2006/10/17 Nat Genet. 2006 Nov;38(11):1269-77. doi: 10.1038/ng1898. Epub 2006 Oct 15.","abstract":"Knockdown of the transcription factor PU.1 (encoded by Sfpi1) leads to acute myeloid leukemia (AML) in mice. We examined the transcriptome of preleukemic hematopoietic stem cells (HSCs) in which PU.1 was knocked down (referred to as 'PU.1-knockdown HSCs') to identify transcriptional changes preceding malignant transformation. Transcription factors c-Jun and JunB were among the top-downregulated targets. Restoration of c-Jun expression in preleukemic cells rescued the PU.1 knockdown-initiated myelomonocytic differentiation block. Lentiviral restoration of JunB at the leukemic stage led to loss of leukemic self-renewal capacity and prevented leukemia in NOD-SCID mice into which leukemic PU.1-knockdown cells were transplanted. Examination of human individuals with AML confirmed the correlation between PU.1 and JunB downregulation. These results delineate a transcriptional pattern that precedes leukemic transformation in PU.1-knockdown HSCs and demonstrate that decreased levels of c-Jun and JunB contribute to the development of PU.1 knockdown-induced AML by blocking differentiation and increasing self-renewal. Therefore, examination of disturbed gene expression in HSCs can identify genes whose dysregulation is essential for leukemic stem cell function and that are targets for therapeutic interventions.","keywords":"Animals Cell Differentiation/genetics Cell Transformation, Neoplastic/genetics Down-Regulation Granulocytes/cytology Hematopoietic Stem Cell Transplantation Hematopoietic Stem Cells/cytology/metabolism/*pathology Humans Leukemia, Myeloid, Acute/*genetics/metabolism/pathology Mice Mice, Inbred NOD Mice, Knockout Mice, SCID Monocytes/cytology Proto-Oncogene Proteins/*genetics/metabolism Proto-Oncogene Proteins c-jun/genetics/metabolism/*physiology Trans-Activators/*genetics/metabolism Transcription, Genetic Transduction, Genetic","issn":"1061-4036 (Print) 1061-4036","doi":"10.1038/ng1898","year":"2006","bibtex":"@article{RN6200,\n author = {Steidl, U. and Rosenbauer, F. and Verhaak, R. G. and Gu, X. and Ebralidze, A. and Otu, H. H. and Klippel, S. and Steidl, C. and Bruns, I. and Costa, D. B. and Wagner, K. and Aivado, M. and Kobbe, G. and Valk, P. J. and Passegué, E. and Libermann, T. A. and Delwel, R. and Tenen, D. G.},\n title = {Essential role of Jun family transcription factors in PU.1 knockdown-induced leukemic stem cells},\n journal = {Nat Genet},\n volume = {38},\n number = {11},\n pages = {1269-77},\n note = {Steidl, Ulrich\nRosenbauer, Frank\nVerhaak, Roel G W\nGu, Xuesong\nEbralidze, Alexander\nOtu, Hasan H\nKlippel, Steffen\nSteidl, Christian\nBruns, Ingmar\nCosta, Daniel B\nWagner, Katharina\nAivado, Manuel\nKobbe, Guido\nValk, Peter J M\nPassegué, Emmanuelle\nLibermann, Towia A\nDelwel, Ruud\nTenen, Daniel G\nCA41456/CA/NCI NIH HHS/United States\nJournal Article\nResearch Support, N.I.H., Extramural\nResearch Support, Non-U.S. Gov't\nUnited States\n2006/10/17\nNat Genet. 2006 Nov;38(11):1269-77. doi: 10.1038/ng1898. Epub 2006 Oct 15.},\n abstract = {Knockdown of the transcription factor PU.1 (encoded by Sfpi1) leads to acute myeloid leukemia (AML) in mice. We examined the transcriptome of preleukemic hematopoietic stem cells (HSCs) in which PU.1 was knocked down (referred to as 'PU.1-knockdown HSCs') to identify transcriptional changes preceding malignant transformation. Transcription factors c-Jun and JunB were among the top-downregulated targets. Restoration of c-Jun expression in preleukemic cells rescued the PU.1 knockdown-initiated myelomonocytic differentiation block. Lentiviral restoration of JunB at the leukemic stage led to loss of leukemic self-renewal capacity and prevented leukemia in NOD-SCID mice into which leukemic PU.1-knockdown cells were transplanted. Examination of human individuals with AML confirmed the correlation between PU.1 and JunB downregulation. These results delineate a transcriptional pattern that precedes leukemic transformation in PU.1-knockdown HSCs and demonstrate that decreased levels of c-Jun and JunB contribute to the development of PU.1 knockdown-induced AML by blocking differentiation and increasing self-renewal. Therefore, examination of disturbed gene expression in HSCs can identify genes whose dysregulation is essential for leukemic stem cell function and that are targets for therapeutic interventions.},\n keywords = {Animals\nCell Differentiation/genetics\nCell Transformation, Neoplastic/genetics\nDown-Regulation\nGranulocytes/cytology\nHematopoietic Stem Cell Transplantation\nHematopoietic Stem Cells/cytology/metabolism/*pathology\nHumans\nLeukemia, Myeloid, Acute/*genetics/metabolism/pathology\nMice\nMice, Inbred NOD\nMice, Knockout\nMice, SCID\nMonocytes/cytology\nProto-Oncogene Proteins/*genetics/metabolism\nProto-Oncogene Proteins c-jun/genetics/metabolism/*physiology\nTrans-Activators/*genetics/metabolism\nTranscription, Genetic\nTransduction, Genetic},\n ISSN = {1061-4036 (Print)\n1061-4036},\n DOI = {10.1038/ng1898},\n year = {2006},\n type = {Journal Article}\n}\n\n","author_short":["Steidl, U.","Rosenbauer, F.","Verhaak, R. G.","Gu, X.","Ebralidze, A.","Otu, H. 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