Photo of Daniel G. Tenen,  MD

Daniel G. Tenen, MD

Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center
Phone: (617) 735-2235
Fax: (617) 735-2222


daniel.tenen@nus.edu.sg

Daniel G. Tenen, MD

Beth Israel Deaconess Medical Center

EDUCATIONAL TITLES

  • Professor, Medicine, Harvard Medical School
  • Professor, Hematology/Oncology, Beth Israel Deaconess Medical Center

DF/HCC PROGRAM AFFILIATION

Research Abstract

Dr. Tenen's laboratory focuses on transcription factors and gene regulation, and their relationship to differentiation. The laboratory has characterized transcription factors which play a role in the differentiation of hematopoietic stem cells into different specific lineages, with particular focus on myeloid (granulocyte and monocyte) differentiation in normal and leukemic cells. The laboratory has isolated and characterized regulatory elements of master transcription factors expressed at different stages of differentiation, including stem and progenitor cells. Our studies have demonstrated a role for these transcription factors in the regulation of expression of important myeloid genes, and knockout studies demonstrated that they play a major role in hematopoietic development. In addition, we have identified mutations and specific abnormalities in expression of these factors in specific subtypes of myeloid leukemias. Part of the current efforts in the laboratory focus on understanding regulation, signal transduction pathways, and interacting partners of these factors, and their role in stem cells in normal hematopoiesis. In addition, a major effort in our laboratory is focused on further characterization of these factors in leukemogenesis, including developing drugs and other therapies specifically aimed at these factors. A related project in the lab is studying the role of transcription factors in normal lung differentiation, as well as in lung cancer. Other basic studies are investigating the role of long noncoding RNAs in gene regulation and chromatin structure. Techniques in the laboratory include analysis of regulation, function, and signaling of transcription factors, transgenic and knockout studies, and gene therapy applications.

Publications

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  • Aikawa Y, Yamagata K, Katsumoto T, Shima Y, Shino M, Stanley ER, Cleary ML, Akashi K, Tenen DG, Kitabayashi I. Essential role of PU.1 in maintenance of mixed lineage leukemia-associated leukemic stem cells. Cancer Sci 2015; 106:227-36. PubMed
  • Adamia S, Bar-Natan M, Haibe-Kains B, Pilarski PM, Bach C, Pevzner S, Calimeri T, Avet-Loiseau H, Lode L, Verselis S, Fox EA, Galinsky I, Mathews S, Dagogo-Jack I, Wadleigh M, Steensma DP, Motyckova G, Deangelo DJ, Quackenbush J, Tenen DG, Stone RM, Griffin JD. NOTCH2 and FLT3 gene mis-splicings are common events in patients with acute myeloid leukemia (AML): new potential targets in AML. Blood 2014. PubMed
  • Chan TH, Lin CH, Qi L, Fei J, Li Y, Yong KJ, Liu M, Song Y, Chow RK, Ng VH, Yuan YF, Tenen DG, Guan XY, Chen L. A disrupted RNA editing balance mediated by ADARs (Adenosine DeAminases that act on RNA) in human hepatocellular carcinoma. Gut 2014; 63:832-43. PubMed
  • Komeno Y, Yan M, Matsuura S, Lam K, Lo MC, Huang YJ, Tenen DG, Downing JR, Zhang DE. Runx1 exon 6 related alternative splicing isoforms differentially regulate hematopoiesis in mice. Blood 2014. PubMed
  • Liss A, Ooi CH, Zjablovskaja P, Benoukraf T, Radomska HS, Ju C, Wu M, Balastik M, Delwel R, Brdicka T, Tan P, Tenen DG, Alberich-Jorda M. The gene signature in CCAAT-enhancer-binding protein 留 dysfunctional acute myeloid leukemia predicts responsiveness to histone deacetylase inhibitors. Haematologica 2014; 99:697-705. PubMed
  • Zhao X, Chen A, Yan X, Zhang Y, He F, Hayashi Y, Dong Y, Rao Y, Li B, Conway RM, Maiques-Diaz A, Elf SE, Huang N, Zuber J, Xiao Z, Tse W, Tenen DG, Wang Q, Chen W, Mulloy JC, Nimer SD, Huang G. Downregulation of RUNX1/CBF硫 by MLL fusion proteins enhances hematopoietic stem cell self-renewal. Blood 2014; 123:1729-38. PubMed
  • Qi L, Chan TH, Tenen DG, Chen L. RNA editome imbalance in hepatocellular carcinoma. Cancer Res 2014; 74:1301-6. PubMed
  • May G, Soneji S, Tipping AJ, Teles J, McGowan SJ, Wu M, Guo Y, Fugazza C, Brown J, Karlsson G, Pina C, Olariu V, Taylor S, Tenen DG, Peterson C, Enver T. Dynamic analysis of gene expression and genome-wide transcription factor binding during lineage specification of multipotent progenitors. Cell Stem Cell 2013; 13:754-68. PubMed
  • Di Ruscio A, Ebralidze AK, Benoukraf T, Amabile G, Goff LA, Terragni J, Figueroa ME, De Figueiredo Pontes LL, Alberich-Jorda M, Zhang P, Wu M, D'Alò F, Melnick A, Leone G, Ebralidze KK, Pradhan S, Rinn JL, Tenen DG. DNMT1-interacting RNAs block gene-specific DNA methylation. Nature 2013; 503:371-6. PubMed
  • Zhang H, Alberich-Jorda M, Amabile G, Yang H, Staber PB, Di Ruscio A, Diruscio A, Welner RS, Ebralidze A, Zhang J, Levantini E, Lefebvre V, Valk PJ, Delwel R, Hoogenkamp M, Nerlov C, Cammenga J, Saez B, Scadden DT, Bonifer C, Ye M, Tenen DG. Sox4 is a key oncogenic target in C/EBP留 mutant acute myeloid leukemia. Cancer Cell 2013; 24:575-88. PubMed
  • Katzerke C, Madan V, Gerloff D, Bräuer-Hartmann D, Hartmann JU, Wurm AA, Müller-Tidow C, Schnittger S, Tenen DG, Niederwieser D, Behre G. Transcription factor C/EBP留-induced microRNA-30c inactivates Notch1 during granulopoiesis and is downregulated in acute myeloid leukemia. Blood 2013; 122:2433-42. PubMed
  • Li A, Yang Y, Gao C, Lu J, Jeong HW, Liu BH, Tang P, Yao X, Neuberg D, Huang G, Tenen DG, Chai L. A SALL4/MLL/HOXA9 pathway in murine and human myeloid leukemogenesis. J Clin Invest 2013; 123:4195-207. PubMed
  • Yong KJ, Chai L, Tenen DG. Oncofetal gene SALL4 in aggressive hepatocellular carcinoma. N Engl J Med 2013; 369:1171-2. PubMed
  • Yong KJ, Gao C, Lim JS, Yan B, Yang H, Dimitrov T, Kawasaki A, Ong CW, Wong KF, Lee S, Ravikumar S, Srivastava S, Tian X, Poon RT, Fan ST, Luk JM, Dan YY, Salto-Tellez M, Chai L, Tenen DG. Oncofetal gene SALL4 in aggressive hepatocellular carcinoma. N Engl J Med 2013; 368:2266-76. PubMed
  • Ye M, Zhang H, Amabile G, Yang H, Staber PB, Zhang P, Levantini E, Alberich-Jordà M, Zhang J, Kawasaki A, Tenen DG. C/EBPa controls acquisition and maintenance of adult haematopoietic stem cell quiescence. Nat Cell Biol 2013; 15:385-94. PubMed
  • Welner RS, Bararia D, Amabile G, Czibere A, Benoukraf T, Bach C, Wansa KD, Ye M, Zhang H, Iino T, Hetherington CJ, Akashi K, Tenen DG. C/EBP留 is required for development of dendritic cell progenitors. Blood 2013. PubMed
  • Staber PB, Zhang P, Ye M, Welner RS, Nombela-Arrieta C, Bach C, Kerenyi M, Bartholdy BA, Zhang H, Alberich-Jordà M, Lee S, Yang H, Ng F, Zhang J, Leddin M, Silberstein LE, Hoefler G, Orkin SH, Göttgens B, Rosenbauer F, Huang G, Tenen DG. Sustained PU.1 levels balance cell-cycle regulators to prevent exhaustion of adult hematopoietic stem cells. Mol Cell 2013; 49:934-46. PubMed
  • Amabile G, Welner RS, Nombela-Arrieta C, D'Alise AM, Di Ruscio A, Ebralidze AK, Kraytsberg Y, Ye M, Kocher O, Neuberg DS, Khrapko K, Silberstein LE, Tenen DG. In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells. Blood 2013; 121:1255-64. PubMed
  • Gao C, Dimitrov T, Yong KJ, Tatetsu H, Jeong HW, Luo HR, Bradner JE, Tenen DG, Chai L. Targeting transcription factor SALL4 in acute myeloid leukemia by interrupting its interaction with an epigenetic complex. Blood 2013; 121:1413-21. PubMed
  • Chen L, Li Y, Lin CH, Chan TH, Chow RK, Song Y, Liu M, Yuan YF, Fu L, Kong KL, Qi L, Li Y, Zhang N, Tong AH, Kwong DL, Man K, Lo CM, Lok S, Tenen DG, Guan XY. Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma. Nat Med 2013; 19:209-16. PubMed
  • Hirai H, Kamio N, Huang G, Matsusue A, Ogino S, Kimura N, Satake S, Ashihara E, Imanishi J, Tenen DG, Maekawa T. Cyclic AMP responsive element binding proteins are involved in 'emergency' granulopoiesis through the upregulation of CCAAT/enhancer binding protein 硫. PLoS ONE 2013; 8:e54862. PubMed
  • Alberich-Jordà M, Wouters B, Balastik M, Shapiro-Koss C, Zhang H, Diruscio A, Radomska HS, Ebralidze AK, Amabile G, Ye M, Zhang J, Lowers I, Avellino R, Melnick A, Figueroa ME, Valk PJ, Delwel R, Tenen DG. C/EBP粒 deregulation results in differentiation arrest in acute myeloid leukemia. J Clin Invest 2012. PubMed
  • Lichtinger M, Ingram R, Hannah R, Müller D, Clarke D, Assi SA, Lie-A-Ling M, Noailles L, Vijayabaskar MS, Wu M, Tenen DG, Westhead DR, Kouskoff V, Lacaud G, Göttgens B, Bonifer C. RUNX1 reshapes the epigenetic landscape at the onset of haematopoiesis. EMBO J 2012; 31:4318-33. PubMed
  • Gao C, Kong NR, Li A, Tatetu H, Ueno S, Yang Y, He J, Yang J, Ma Y, Kao GS, Tenen DG, Chai L. SALL4 is a key transcription regulator in normal human hematopoiesis. Transfusion 2012. PubMed
  • Zhang Y, Yan X, Sashida G, Zhao X, Rao Y, Goyama S, Whitman SP, Zorko N, Bernot K, Conway RM, Witte D, Wang QF, Tenen DG, Xiao Z, Marcucci G, Mulloy JC, Grimes HL, Caligiuri MA, Huang G. Stress hematopoiesis reveals abnormal control of self-renewal, lineage bias, and myeloid differentiation in Mll partial tandem duplication (Mll-PTD) hematopoietic stem/progenitor cells. Blood 2012; 120:1118-29. PubMed
  • Radomska HS, Alberich-Jordà M, Will B, Gonzalez D, Delwel R, Tenen DG. Targeting CDK1 promotes FLT3-activated acute myeloid leukemia differentiation through C/EBP留. J Clin Invest 2012; 122:2955-66. PubMed
  • Leddin M, Perrod C, Hoogenkamp M, Ghani S, Assi S, Heinz S, Wilson NK, Follows G, Schönheit J, Vockentanz L, Mosammam AM, Chen W, Tenen DG, Westhead DR, Göttgens B, Bonifer C, Rosenbauer F. Two distinct auto-regulatory loops operate at the PU.1 locus in B cells and myeloid cells. Blood 2011; 117:2827-38. PubMed
  • Jiang S, Alberich-Jorda M, Zagozdzon R, Parmar K, Fu Y, Mauch P, Banu N, Makriyannis A, Tenen DG, Avraham S, Groopman JE, Avraham HK. Cannabinoid receptor 2 and its agonists mediate hematopoiesis and hematopoietic stem and progenitor cell mobilization. Blood 2011; 117:827-38. PubMed
  • Pulikkan JA, Peramangalam PS, Dengler V, Ho PA, Preudhomme C, Meshinchi S, Christopeit M, Nibourel O, Müller-Tidow C, Bohlander SK, Tenen DG, Behre G. C/EBP{alpha}-regulated microRNA-34a targets E2F3 during granulopoiesis and is downregulated in AML with CEBPA mutations. Blood 2010; 116:5638-49. PubMed
  • Yeo WL, Riely GJ, Yeap BY, Lau MW, Warner JL, Bodio K, Huberman MS, Kris MG, Tenen DG, Pao W, Kobayashi S, Costa DB. Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations. J Thorac Oncol 2010; 5:1048-53. PubMed
  • O'Brien KB, Alberich-Jordà M, Yadav N, Kocher O, Diruscio A, Ebralidze A, Levantini E, Sng NJ, Bhasin M, Caron T, Kim D, Steidl U, Huang G, Halmos B, Rodig SJ, Bedford MT, Tenen DG, Kobayashi S. CARM1 is required for proper control of proliferation and differentiation of pulmonary epithelial cells. Development 2010; 137:2147-56. PubMed
  • Aikawa Y, Katsumoto T, Zhang P, Shima H, Shino M, Terui K, Ito E, Ohno H, Stanley ER, Singh H, Tenen DG, Kitabayashi I. PU.1-mediated upregulation of CSF1R is crucial for leukemia stem cell potential induced by MOZ-TIF2. Nat Med 2010; 16:580-5, 1p following 585. PubMed
  • Schemionek M, Elling C, Steidl U, Baumer N, Hamilton A, Spieker T, Gothert JR, Stehling M, Wagers A, Huettner CS, Tenen DG, Tickenbrock L, Berdel WE, Serve H, Holyoake TL, Muller-Tidow C, Koschmieder S. BCR-ABL enhances differentiation of long-term repopulating hematopoietic stem cells. Blood 2010; 115:3185-95. PubMed
  • Will B, Siddiqi T, Alberich Jordà M, Shimamura T, Luptakova K, Staber PB, Costa DB, Steidl U, Tenen DG, Kobayashi S. Apoptosis induced by JAK2 inhibition is mediated by Bim and enhanced by the BH3 mimetic ABT-737 in JAK2 mutant human erythroid cells. Blood 2010; 115:2901-9. PubMed
  • Kamio N, Hirai H, Ashihara E, Tenen DG, Maekawa T, Imanishi J. Use of bicistronic vectors in combination with flow cytometry to screen for effective small interfering RNA target sequences. Biochem Biophys Res Commun 2010; 393:498-503. PubMed
  • Pulikkan JA, Dengler V, Peramangalam PS, Peer Zada AA, Müller-Tidow C, Bohlander SK, Tenen DG, Behre G. Cell-cycle regulator E2F1 and microRNA-223 comprise an autoregulatory negative feedback loop in acute myeloid leukemia. Blood 2010; 115:1768-78. PubMed
  • Guibal FC, Alberich-Jorda M, Hirai H, Ebralidze A, Levantini E, Di Ruscio A, Zhang P, Santana-Lemos BA, Neuberg D, Wagers AJ, Rego EM, Tenen DG. Identification of a myeloid committed progenitor as the cancer-initiating cell in acute promyelocytic leukemia. Blood 2009; 114:5415-25. PubMed
  • Wojiski S, Guibal FC, Kindler T, Lee BH, Jesneck JL, Fabian A, Tenen DG, Gilliland DG. PML-RARalpha initiates leukemia by conferring properties of self-renewal to committed promyelocytic progenitors. Leukemia 2009; 23:1462-71. PubMed
  • Hoogenkamp M,Lichtinger M,Krysinska H,Lancrin C,Clarke D,Williamson A,Mazzarella L,Ingram R,Jorgensen H,Fisher A,Tenen DG,Kouskoff V,Lacaud G,Bonifer C. Early chromatin unfolding by RUNX1 - a molecular explanation for differential requirements during specification versus maintenance of the hematopoietic gene expression program. Blood 2009; 114:299-309. PubMed
  • Naumov GN,Nilsson MB,Cascone T,Briggs A,Straume O,Akslen LA,Lifshits E,Byers LA,Xu L,Wu HK,Janne P,Kobayashi S,Halmos B,Tenen D,Tang XM,Engelman J,Yeap B,Folkman J,Johnson BE,Heymach JV. Combined vascular endothelial growth factor receptor and epidermal growth factor receptor (EGFR) blockade inhibits tumor growth in xenograft models of EGFR inhibitor resistance. Clin Cancer Res 2009; 15:3484-94. PubMed
  • Koschmieder S,Halmos B,Levantini E,Tenen DG. Dysregulation of the C/EBPalpha differentiation pathway in human cancer. J Clin Oncol 2008; 27:619-28. PubMed
  • Costa DB,Nguyen KS,Cho BC,Sequist LV,Jackman DM,Riely GJ,Yeap BY,Halmos B,Kim JH,Janne PA,Huberman MS,Pao W,Tenen DG,Kobayashi S. Effects of erlotinib in EGFR mutated non-small cell lung cancers with resistance to gefitinib. Clin Cancer Res 2008; 14:7060-7. PubMed
  • Ebralidze AK,Guibal FC,Steidl U,Zhang P,Lee S,Bartholdy B,Jorda MA,Petkova V,Rosenbauer F,Huang G,Dayaram T,Klupp J,O'Brien KB,Will B,Hoogenkamp M,Borden KL,Bonifer C,Tenen DG. PU.1 expression is modulated by the balance of functional sense and antisense RNAs regulated by a shared cis-regulatory element. Genes Dev 2008; 22:2085-92. PubMed
  • Shimamura T,Li D,Ji H,Haringsma HJ,Liniker E,Borgman CL,Lowell AM,Minami Y,McNamara K,Perera SA,Zaghlul S,Thomas RK,Greulich H,Kobayashi S,Chirieac LR,Padera RF,Kubo S,Takahashi M,Tenen DG,Meyerson M,Wong KK,Shapiro GI. Hsp90 inhibition suppresses mutant EGFR-T790M signaling and overcomes kinase inhibitor resistance. Cancer Res 2008; 68:5827-38. PubMed
  • Huang G,Eisenberg R,Yan M,Monti S,Lawrence E,Fu P,Walbroehl J,Lowenberg E,Golub T,Merchan J,Tenen DG,Markowitz SD,Halmos B. 15-Hydroxyprostaglandin dehydrogenase is a target of hepatocyte nuclear factor 3beta and a tumor suppressor in lung cancer. Cancer Res 2008; 68:5040-8. PubMed
  • Kirstetter P, Schuster MB, Bereshchenko O, Moore S, Dvinge H, Kurz E, Theilgaard-Monch K, Mansson R, Pedersen TA, Pabst T, Schrock E, Porse BT, Jacobsen SE, Bertone P, Tenen DG, Nerlov C. Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells. Cancer Cell 2008; 13:299-310. PubMed
  • Bruns I, Steidl U, Fischer JC, Czibere A, Kobbe G, Raschke S, Singh R, Fenk R, Rosskopf M, Pechtel S, von Haeseler A, Wernet P, Tenen DG, Haas R, Kronenwett R. Pegylated granulocyte colony-stimulating factor mobilizes CD34+ cells with different stem and progenitor subsets and distinct functional properties in comparison with unconjugated granulocyte colony-stimulating factor. Haematologica 2008; 93:347-55. PubMed
  • Costa DB, Schumer ST, Tenen DG, Kobayashi S. Differential responses to erlotinib in epidermal growth factor receptor (EGFR)-mutated lung cancers with acquired resistance to gefitinib carrying the L747S or T790M secondary mutations. J Clin Oncol 2008; 26:1182-4; author reply 1184-6. PubMed
  • van Wageningen S, Breems-de Ridder MC, Nigten J, Nikoloski G, Erpelinck-Verschueren CA, Lowenberg B, de Witte T, Tenen DG, van der Reijden BA, Jansen JH. Gene transactivation without direct DNA binding defines a novel gain-of-function for PML-RARalpha. Blood 2007; 111:1634-43. PubMed
  • Huang G, Zhang P, Hirai H, Elf S, Yan X, Chen Z, Koschmieder S, Okuno Y, Dayaram T, Growney JD, Shivdasani RA, Gilliland DG, Speck NA, Nimer SD, Tenen DG. PU.1 is a major downstream target of AML1 (RUNX1) in adult mouse hematopoiesis. Nat Genet 2007; 40:51-60. PubMed
  • Wouters BJ, Jorda MA, Keeshan K, Louwers I, Erpelinck-Verschueren CA, Tielemans D, Langerak AW, He Y, Yashiro-Ohtani Y, Zhang P, Hetherington CJ, Verhaak RG, Valk PJ, Lowenberg B, Tenen DG, Pear WS, Delwel R. Distinct gene expression profiles of acute myeloid/T-lymphoid leukemia with silenced CEBPA and mutations in NOTCH1. Blood 2007; 110:3706-14. PubMed
  • Koschmieder S, D'Alo F, Radomska H, Schoneich C, Chang JS, Konopleva M, Kobayashi S, Levantini E, Suh N, Di Ruscio A, Voso MT, Watt JC, Santhanam R, Sargin B, Kantarjian H, Andreeff M, Sporn MB, Perrotti D, Berdel WE, Muller-Tidow C, Serve H, Tenen DG. CDDO induces granulocytic differentiation of myeloid leukemic blasts through translational up-regulation of p42 CCAAT enhancer binding protein alpha. Blood 2007; 110:3695-705. PubMed
  • Geletu M, Balkhi MY, Peer Zada AA, Christopeit M, Pulikkan JA, Trivedi AK, Tenen DG, Behre G. Target proteins of C/EBPalphap30 in AML: C/EBPalphap30 enhances sumoylation of C/EBPalphap42 via up-regulation of Ubc9. Blood 2007; 110:3301-9. PubMed
  • Yeamans C, Wang D, Paz-Priel I, Torbett BE, Tenen DG, Friedman AD. C/EBPalpha binds and activates the PU.1 distal enhancer to induce monocyte lineage commitment. Blood 2007; 110:3136-42. PubMed
  • Hoogenkamp M, Krysinska H, Ingram R, Huang G, Barlow R, Clarke D, Ebralidze A, Zhang P, Tagoh H, Cockerill PN, Tenen DG, Bonifer C. The Pu.1 locus is differentially regulated at the level of chromatin structure and noncoding transcription by alternate mechanisms at distinct developmental stages of hematopoiesis. Mol Cell Biol 2007; 27:7425-38. PubMed
  • Yu Z, Boggon TJ, Kobayashi S, Jin C, Ma PC, Dowlati A, Kern JA, Tenen DG, Halmos B. Resistance to an irreversible epidermal growth factor receptor (EGFR) inhibitor in EGFR-mutant lung cancer reveals novel treatment strategies. Cancer Res 2007; 67:10417-27. PubMed
  • Costa DB, Halmos B, Kumar A, Schumer ST, Huberman MS, Boggon TJ, Tenen DG, Kobayashi S. BIM mediates EGFR tyrosine kinase inhibitor-induced apoptosis in lung cancers with oncogenic EGFR mutations. PLoS Med 2007; 4:1669-79; discussion 1680. PubMed
  • Costa DB, Kobayashi S, Tenen DG, Huberman MS. Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non-small cell lung cancers. Lung Cancer 2007; 58:95-103. PubMed
  • Steidl U, Steidl C, Ebralidze A, Chapuy B, Han HJ, Will B, Rosenbauer F, Becker A, Wagner K, Koschmieder S, Kobayashi S, Costa DB, Schulz T, O'Brien KB, Verhaak RG, Delwel R, Haase D, Trumper L, Krauter J, Kohwi-Shigematsu T, Griesinger F, Tenen DG. A distal single nucleotide polymorphism alters long-range regulation of the PU.1 gene in acute myeloid leukemia. J Clin Invest 2007; 117:2611-20. PubMed
  • Tatetsu H, Ueno S, Hata H, Yamada Y, Takeya M, Mitsuya H, Tenen DG, Okuno Y. Down-regulation of PU.1 by methylation of distal regulatory elements and the promoter is required for myeloma cell growth. Cancer Res 2007; 67:5328-36. PubMed
  • Costa DB, Li S, Kocher O, Feins RH, Keller SM, Schiller JH, Johnson DH, Tenen DG, Halmos B. Immunohistochemical analysis of C/EBPalpha in non-small cell lung cancer reveals frequent down-regulation in stage II and IIIA tumors: A correlative study of E3590. Lung Cancer 2007; 56:97-103. PubMed
  • Kobayashi S, Shimamura T, Monti S, Steidl U, Hetherington CJ, Lowell AM, Golub T, Meyerson M, Tenen DG, Shapiro GI, Halmos B. Transcriptional profiling identifies cyclin D1 as a critical downstream effector of mutant epidermal growth factor receptor signaling. Cancer Res 2006; 66:11389-98. PubMed
  • Zada AA, Geletu MH, Pulikkan JA, M. Proteomic analysis of acute promyelocytic leukemia: PML-RARalpha leads to decreased phosphorylation of OP18 at serine 63. Proteomics 2006; 6:5705-19. PubMed
  • Iwasaki H, Mizuno S, Arinobu Y, Ozawa H, Mori Y, Shigematsu H, Takatsu K, Tenen DG, Akashi K. The order of expression of transcription factors directs hierarchical specification of hematopoietic lineages. Genes Dev 2006; 20:3010-21. PubMed
  • Steidl U, Rosenbauer F, Verhaak RG, Gu X, Ebralidze A, Otu HH, Klippel S, Steidl C, Bruns I, Costa DB, Wagner K, Aivado M, Kobbe G, Valk PJ, Passegu. Essential role of Jun family transcription factors in PU.1 knockdown-induced leukemic stem cells. Nat Genet 2006; 38:1269-77. PubMed
  • Lee YJ, Jones LC, Timchenko NA, Perrotti D, Tenen DG, Kogan SC. CCAAT/enhancer binding proteins alpha and epsilon cooperate with all-trans retinoic acid in therapy but differ in their antileukemic activities. Blood 2006; 108:2416-9. PubMed
  • Kubo S, Levantini E, Kobayashi S, Kocher O, Halmos B, Tenen DG, Takahashi M. Three-dimensional magnetic resonance microscopy of pulmonary solitary tumors in transgenic mice. Magn Reson Med 2006; 56:698-703. PubMed
  • Costa DB, Dayaram T, D'Alo F, Wouters BJ, Tenen DG, Meyerson M, Tsao MS, Halmos B. C/EBPalpha mutations in lung cancer. Lung Cancer 2006; 53:253-4. PubMed
  • Hirai H, Zhang P, Dayaram T, Hetherington CJ, Mizuno S, Imanishi J, Akashi K, Tenen DG. C/EBPbeta is required for 'emergency' granulopoiesis. Nat Immunol 2006; 7:732-9. PubMed
  • Mueller BU, Pabst T, Hauser P, Gilliland G, Neuberg D, Tenen DG. Mutations of the transcription factor PU.1 are not associated with acute lymphoblastic leukaemia. Br J Cancer 2006; 94:1918-20. PubMed
  • Ji H, Li D, Chen L, Shimamura T, Kobayashi S, McNamara K, Mahmood U, Mitchell A, Sun Y, Al-Hashem R, Chirieac LR, Padera R, Bronson RT, Kim W, J. The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies. Cancer Cell 2006; 9:485-95. PubMed
  • Pabst T, Stillner E, Neuberg D, Nimer S, Willman CL, List AF, Melo JV, Tenen DG, Mueller BU. Mutations of the myeloid transcription factor CEBPA are not associated with the blast crisis of chronic myeloid leukaemia. Br J Haematol 2006; 133:400-2. PubMed
  • Wagner K, Zhang P, Rosenbauer F, Drescher B, Kobayashi S, Radomska HS, Kutok JL, Gilliland DG, Krauter J, Tenen DG. Absence of the transcription factor CCAAT enhancer binding protein alpha results in loss of myeloid identity in bcr/abl-induced malignancy. Proc Natl Acad Sci U S A 2006; 103:6338-43. PubMed
  • Mueller BU, Pabst T, Fos J, Petkovic V, Fey MF, Asou N, Buergi U, Tenen DG. ATRA resolves the differentiation block in t(15;17) acute myeloid leukemia by restoring PU.1 expression. Blood 2005; 107:3330-8. PubMed
  • Radomska HS, Bass. Block of C/EBP alpha function by phosphorylation in acute myeloid leukemia with FLT3 activating mutations. J Exp Med 2006; 203:371-81. PubMed
  • Bass. Respiratory failure due to differentiation arrest and expansion of alveolar cells following lung-specific loss of the transcription factor C/EBPalpha in mice. Mol Cell Biol 2006; 26:1109-23. PubMed
  • Rosenbauer F, Owens BM, Yu L, Tumang JR, Steidl U, Kutok JL, Clayton LK, Wagner K, Scheller M, Iwasaki H, Liu C, Hackanson B, Akashi K, Leutz A, Rothstein TL, Plass C, Tenen DG. Lymphoid cell growth and transformation are suppressed by a key regulatory element of the gene encoding PU.1. Nat Genet 2005; 38:27-37. PubMed
  • Arinobu Y, Iwasaki H, Gurish MF, Mizuno S, Shigematsu H, Ozawa H, Tenen DG, Austen KF, Akashi K. Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis. Proc Natl Acad Sci U S A 2005; 102:18105-10. PubMed
  • Iwasaki H, Somoza C, Shigematsu H, Duprez EA, Iwasaki-Arai J, Mizuno S, Arinobu Y, Geary K, Zhang P, Dayaram T, Fenyus ML, Elf S, Chan S, Kastner P, Huettner CS, Murray R, Tenen DG, Akashi K. Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation. Blood 2005; 106:1590-600. PubMed
  • Mukohara T, Engelman JA, Hanna NH, Yeap BY, Kobayashi S, Lindeman N, Halmos B, Pearlberg J, Tsuchihashi Z, Cantley LC, Tenen DG, Johnson BE, J. Differential effects of gefitinib and cetuximab on non-small-cell lung cancers bearing epidermal growth factor receptor mutations. J Natl Cancer Inst 2005; 97:1185-94. PubMed
  • Koschmieder S, Rosenbauer F, Steidl U, Owens BM, Tenen DG. Role of transcription factors C/EBPalpha and PU.1 in normal hematopoiesis and leukemia. Int J Hematol 2005; 81:368-77. PubMed
  • Okuno Y, Huang G, Rosenbauer F, Evans EK, Radomska HS, Iwasaki H, Akashi K, Moreau-Gachelin F, Li Y, Zhang P, G. Potential autoregulation of transcription factor PU.1 by an upstream regulatory element. Mol Cell Biol 2005; 25:2832-45. PubMed
  • Kobayashi S, Boggon TJ, Dayaram T, J. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 2005; 352:786-92. PubMed
  • Koschmieder S, Goettgens B, Zhang P, Iwasaki-Arai J, Akashi K, Kutok JL, Dayaram T, Geary K, Green AR, Tenen DG, Huettner CS. Inducible chronic phase of myeloid leukemia with expansion of hematopoietic stem cells in a transgenic model of BCR-ABL leukemogenesis. Blood 2004; 105:324-34. PubMed
  • Cho D, Kocher O, Lee JC, Tenen DG, Meyerson ML, Janne PA, Halmos B. Unusual cases in multiple myeloma and a dramatic response in metastatic lung cancer: case 4. Mutation of the epidermal growth factor receptor in an elderly man with advanced, gefitinib-responsive, non-small-cell lung cancer. J Clin Oncol 2004; 23:235-7. PubMed
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  • Rosenbauer F, Wagner K, Zhang P, Knobeloch KP, Iwama A, Tenen DG. pDP4, a novel glycoprotein secreted by mature granulocytes, is regulated by transcription factor PU.1. Blood 2004; 103:4294-301. PubMed
  • Rosenbauer F, Wagner K, Kutok JL, Iwasaki H, Le Beau MM, Okuno Y, Akashi K, Fiering S, Tenen DG. Acute myeloid leukemia induced by graded reduction of a lineage-specific transcription factor, PU.1. Nat Genet 2004; 36:624-30. PubMed
  • Ross SE, Radomska HS, Wu B, Zhang P, Winnay JN, Bajnok L, Wright WS, Schaufele F, Tenen DG, MacDougald OA. Phosphorylation of C/EBPalpha inhibits granulopoiesis. Mol Cell Biol 2004; 24:675-86. PubMed
  • Huettner CS, Koschmieder S, Iwasaki H, Iwasaki-Arai J, Radomska HS, Akashi K, Tenen DG. Inducible expression of BCR/ABL using human CD34 regulatory elements results in a megakaryocytic myeloproliferative syndrome. Blood 2003; 102:3363-70. PubMed
  • Els. The fusion protein AML1-ETO in acute myeloid leukemia with translocation t(8;21) induces c-jun protein expression via the proximal AP-1 site of the c-jun promoter in an indirect, JNK-dependent manner. Oncogene 2003; 22:5646-57. PubMed
  • Rangatia J, Vangala RK, Singh SM, Peer Zada AA, Els. Elevated c-Jun expression in acute myeloid leukemias inhibits C/EBPalpha DNA binding via leucine zipper domain interaction. Oncogene 2003; 22:4760-4. PubMed
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  • Mueller BU, Pabst T, Osato M, Asou N, Johansen LM, Minden MD, Behre G, Hiddemann W, Ito Y, Tenen DG. Heterozygous PU.1 mutations are associated with acute myeloid leukemia. Blood 2003; 101:2074. PubMed
  • Truong BT, Lee YJ, Lodie TA, Park DJ, Perrotti D, Watanabe N, Koeffler HP, Nakajima H, Tenen DG, Kogan SC. CCAAT/Enhancer binding proteins repress the leukemic phenotype of acute myeloid leukemia. Blood 2002; 101:1141-8. PubMed
  • Vangala RK, Heiss-Neumann MS, Rangatia JS, Singh SM, Schoch C, Tenen DG, Hiddemann W, Behre G. The myeloid master regulator transcription factor PU.1 is inactivated by AML1-ETO in t(8;21) myeloid leukemia. Blood 2002; 101:270-7. PubMed
  • van Waalwijk van Doorn-Khosrovani SB, Erpelinck C, Meijer J, van Oosterhoud S, van Putten WL, Valk PJ, Berna Beverloo H, Tenen DG, L. Biallelic mutations in the CEBPA gene and low CEBPA expression levels as prognostic markers in intermediate-risk AML. Hematol J 2003; 4:31-40. PubMed
  • Radomska HS, Gonzalez DA, Okuno Y, Iwasaki H, Nagy A, Akashi K, Tenen DG, Huettner CS. Transgenic targeting with regulatory elements of the human CD34 gene. Blood 2002; 100:4410-9. PubMed
  • Okuno Y, Huettner CS, Radomska HS, Petkova V, Iwasaki H, Akashi K, Tenen DG. Distal elements are critical for human CD34 expression in vivo. Blood 2002; 100:4420-6. PubMed
  • Rangatia J, Vangala RK, Treiber N, Zhang P, Radomska H, Tenen DG, Hiddemann W, Behre G. Downregulation of c-Jun expression by transcription factor C/EBPalpha is critical for granulocytic lineage commitment. Mol Cell Biol 2002; 22:8681-94. PubMed
  • Mayerhofer M, Valent P, Sperr WR, Griffin JD, Sillaber C. 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 2002; 100:3767-75. PubMed
  • Welm AL, Timchenko NA, Ono Y, Sorimachi H, Radomska HS, Tenen DG, Lekstrom-Himes J, Darlington GJ. C/EBPalpha is required for proteolytic cleavage of cyclin A by calpain 3 in myeloid precursor cells. J Biol Chem 2002; 277:33848-56. PubMed
  • Mueller BU, Pabst T, Osato M, Asou N, Johansen LM, Minden MD, Behre G, Hiddemann W, Ito Y, Tenen DG. Heterozygous PU.1 mutations are associated with acute myeloid leukemia. Blood 2002; 100:998-1007. PubMed
  • Behre G, Singh SM, Liu H, Bortolin LT, Christopeit M, Radomska HS, Rangatia J, Hiddemann W, Friedman AD, Tenen DG. Ras signaling enhances the activity of C/EBP alpha to induce granulocytic differentiation by phosphorylation of serine 248. J Biol Chem 2002; 277:26293-9. PubMed
  • Reddy VA, Iwama A, Iotzova G, Schulz M, Elsasser A, Vangala RK, Tenen DG, Hiddemann W, Behre G. Granulocyte inducer C/EBPalpha inactivates the myeloid master regulator PU.1: possible role in lineage commitment decisions. Blood 2002; 100:483-90. PubMed
  • Zhang P, Nelson E, Radomska HS, Iwasaki-Arai J, Akashi K, Friedman AD, Tenen DG. Induction of granulocytic differentiation by 2 pathways. Blood 2002; 99:4406-12. PubMed
  • Okuno Y, Iwasaki H, Huettner CS, Radomska HS, Gonzalez DA, Tenen DG, Akashi K. Differential regulation of the human and murine CD34 genes in hematopoietic stem cells. Proc Natl Acad Sci U S A 2002; 99:6246-51. PubMed
  • Iwama A, Osawa M, Hirasawa R, Uchiyama N, Kaneko S, Onodera M, Shibuya K, Shibuya A, Vinson C, Tenen DG, Nakauchi H. Reciprocal roles for CCAAT/enhancer binding protein (C/EBP) and PU.1 transcription factors in Langerhans cell commitment. J Exp Med 2002; 195:547-58. PubMed
  • Halmos B, Huettner CS, Kocher O, Ferenczi K, Karp DD, Tenen DG. Down-regulation and antiproliferative role of C/EBPalpha in lung cancer. Cancer Res 2002; 62:528-34. PubMed
  • Burel SA, Harakawa N, Zhou L, Pabst T, Tenen DG, Zhang DE. Dichotomy of AML1-ETO functions: growth arrest versus block of differentiation. Mol Cell Biol 2001; 21:5577-90. PubMed
  • Johansen LM, Iwama A, Lodie TA, Sasaki K, Felsher DW, Golub TR, Tenen DG. c-Myc is a critical target for c/EBPalpha in granulopoiesis. Mol Cell Biol 2001; 21:3789-806. PubMed
  • Pabst T, Mueller BU, Harakawa N, Schoch C, Haferlach T, Behre G, Hiddemann W, Zhang DE, Tenen DG. AML1-ETO downregulates the granulocytic differentiation factor C/EBPalpha in t(8;21) myeloid leukemia. Nat Med 2001; 7:444-51. PubMed
  • Pabst T, Mueller BU, Zhang P, Radomska HS, Narravula S, Schnittger S, Behre G, Hiddemann W, Tenen DG. Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding protein-alpha (C/EBPalpha), in acute myeloid leukemia. Nat Genet 2001; 27:263-70. PubMed
  • Zhang P, Zhang X, Iwama A, Yu C, Smith KA, Mueller BU, Narravula S, Torbett BE, Orkin SH, Tenen DG. PU.1 inhibits GATA-1 function and erythroid differentiation by blocking GATA-1 DNA binding. Blood 2000; 96:2641-8. PubMed
  • Rhoades KL, Hetherington CJ, Harakawa N, Yergeau DA, Zhou L, Liu LQ, Little MT, Tenen DG, Zhang DE. Analysis of the role of AML1-ETO in leukemogenesis, using an inducible transgenic mouse model. Blood 2000; 96:2108-15. PubMed
  • Huettner CS, Zhang P, Van Etten RA, Tenen DG. Reversibility of acute B-cell leukaemia induced by BCR-ABL1. Nat Genet 1999; 24:57-60. PubMed
  • Radomska HS, Huettner CS, Zhang P, Cheng T, Scadden DT, Tenen DG. CCAAT/enhancer binding protein alpha is a regulatory switch sufficient for induction of granulocytic development from bipotential myeloid progenitors. Mol Cell Biol 1998; 18:4301-14. PubMed
  • Chen HM, Gonzalez DA, Radomska HS, Voso MT, Sun Z, Zhang P, Zhang DE, Tenen DG. Two promoters direct expression of the murine Spi-B gene, an Ets family transcription factor. Gene 1998; 207:209-18. PubMed
  • Su GH, Chen HM, Muthusamy N, Garrett-Sinha LA, Baunoch D, Tenen DG, Simon MC. Defective B cell receptor-mediated responses in mice lacking the Ets protein, Spi-B. EMBO J 1998; 16:7118-29. PubMed
  • Yergeau DA, Hetherington CJ, Wang Q, Zhang P, Sharpe AH, Binder M, Mar. Embryonic lethality and impairment of haematopoiesis in mice heterozygous for an AML1-ETO fusion gene. Nat Genet 1997; 15:303-6. PubMed
  • Zhang DE, Zhang P, Wang ND, Hetherington CJ, Darlington GJ, Tenen DG. Absence of granulocyte colony-stimulating factor signaling and neutrophil development in CCAAT enhancer binding protein alpha-deficient mice. Proc Natl Acad Sci U S A 1997; 94:569-74. PubMed
  • Cheng T, Shen H, Giokas D, Gere J, Tenen DG, Scadden DT. Temporal mapping of gene expression levels during the differentiation of individual primary hematopoietic cells. Proc Natl Acad Sci U S A 1996; 93:13158-63. PubMed
  • Zhang DE, Hetherington CJ, Meyers S, Rhoades KL, Larson CJ, Chen HM, Hiebert SW, Tenen DG. CCAAT enhancer-binding protein (C/EBP) and AML1 (CBF alpha2) synergistically activate the macrophage colony-stimulating factor receptor promoter. Mol Cell Biol 1996; 16:1231-40. PubMed
  • Zhang DE, Hohaus S, Voso MT, Chen HM, Smith LT, Hetherington CJ, Tenen DG. Function of PU.1 (Spi-1), C/EBP, and AML1 in early myelopoiesis: regulation of multiple myeloid CSF receptor promoters. Curr Top Microbiol Immunol 1996; 211:137-47. PubMed
  • Chen HM, Zhang P, Voso MT, Hohaus S, Gonzalez DA, Glass CK, Zhang DE, Tenen DG. Neutrophils and monocytes express high levels of PU.1 (Spi-1) but not Spi-B. Blood 1995; 85:2918-28. PubMed
  • Dziennis S, Van Etten RA, Pahl HL, Morris DL, Rothstein TL, Blosch CM, Perlmutter RM, Tenen DG. The CD11b promoter directs high-level expression of reporter genes in macrophages in transgenic mice. Blood 1995; 85:319-29. PubMed
  • Zhang DE, Fujioka K, Hetherington CJ, Shapiro LH, Chen HM, Look AT, Tenen DG. Identification of a region which directs the monocytic activity of the colony-stimulating factor 1 (macrophage colony-stimulating factor) receptor promoter and binds PEBP2/CBF (AML1). Mol Cell Biol 1994; 14:8085-95. PubMed
  • Zhang DE, Hetherington CJ, Gonzalez DA, Chen HM, Tenen DG. Regulation of CD14 expression during monocytic differentiation induced with 1 alpha,25-dihydroxyvitamin D3. J Immunol 1994; 153:3276-84. PubMed
  • Voso MT, Burn TC, Wulf G, Lim B, Leone G, Tenen DG. Inhibition of hematopoiesis by competitive binding of transcription factor PU.1. Proc Natl Acad Sci U S A 1994; 91:7932-6. PubMed
  • Zhang DE, Hetherington CJ, Chen HM, Tenen DG. The macrophage transcription factor PU.1 directs tissue-specific expression of the macrophage colony-stimulating factor receptor. Mol Cell Biol 1994; 14:373-81. PubMed
  • Mastrianni DM, Tung NM, Tenen DG. Acute myelogenous leukemia: current treatment and future directions. Am J Med 1992; 92:286-95. PubMed
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