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Graphical AbstractEzh2 Controls an Early Hematopoietic Program and Growth Survival Signaling in Early T Cell Precursor Acute Lymphoblastic Leukemia

Danis et al. developed a genetically engineered mouse model of early T cell precursor acute lymphoblastic leukemia. In comparing leukemia with and without genetic inactivation of Polycomb repressive complex 2 (PRC2) components, the authors show that compromised PRC2 function increases transcription of early hematopoietic programs and leads to enhanced JAK/STAT signaling.


MLL1 and DOT1L cooperate with meningioma-1 to induce acute myeloid leukemia. 

Riedel SS, Haladyna J, Bezzant M, Stevens B, Pollyea DA, Sinha AU, Armstrong SA, Wei Q, Pollock RM, Daigle SR, Jordan CT, Ernst P, Neff T and Bernt KM. J Clin Invest. 2016. doi:10.1172/JCI80825. Epub 2016 Feb 29.

Ezh2 Controls an Early Hematopoietic Program and Growth and Survival Signaling in Early T Cell Precursor Acute Lymphoblastic Leukemia.

Danis E, Yamauchi T, Echanique K, Zhang X, Haladyna J, Riedel SS, Zhu N, Xie H,Orkin SH, Armstrong SA, Bernt KM, Neff T. Cell Rep. 2016 Feb 16. pii: S2211-1247(16)30057-2. doi: 10.1016/j.celrep.2016.01.064. Epub 2016 Feb 18.

Inactivation of Eed impedes MLL-AF9-mediated leukemogenesis through Cdkn2a-dependent and Cdkn2a-independent mechanisms in a murine model.

Danis E, Yamauchi T, Echanique K, Haladyna J, Kalkur R, Riedel S, Zhu N, Xie H, Bernt KM, Orkin SH, Armstrong SA, Neff T
Exp Hematol. 2015 Jun 26. pii: S0301-472X(15)00213-1. doi: 10.1016/j.exphem. Epub 2015 Jun 5.

Mapping Cellular Hierarchy by Single-Cell Analysis of the Cell Surface Repertoire.

Guo G, Luc S, Marco E, Lin TW, Peng C, Kerenyi MA, Beyaz S, Kim W, Xu J, Das PP, Neff T, Zou K, Yuan GC, Orkin SH
Cell Stem Cell. 2013 Oct 3;13(4):492-505. doi: 10.1016/j.stem.2013.07.017. Epub 2013 Sep 12.

Targeted disruption of the EZH2-EED complex inhibits EZH2-dependent cancer.

Kim W, Bird GH, Neff T, Guo G, Kerenyi MA, Walensky LD, Orkin SH
Nat Chem Biol. 2013 Oct;9(10):643-50. doi: 10.1038/nchembio.1331. Epub 2013 Aug 25.

Extended Survival of Glioblastoma Patients with Dynamic Clonal Fluctuations After Chemoprotective Hematopoietic Stem Cell Gene Therapy.

Adair JE, Beard BC, Trobridge GD, Neff T, Rockhill JK, Silbergeld DL, Mrugala M, Kiem HP
Sci Transl Med 9 May 2012 4:133ra57

Genetic and Pharmacologic Inhibition of β-Catenin Targets Imatinib-Resistant Leukemia Stem Cells in CML.

Heidel FH, Bullinger L, Feng Z, Wang Z, Neff TA, Stein L, Kalaitzidis D, Lane SW, Armstrong SA
Cell Stem Cell. 2012 Apr 6; 10(4):412-24

The Polycomb Repressive Complex 2 Is Required For MLL-AF9 Leukemia.

Neff T, Sinha AU, Kluk MJ, Zhu N, Khattab MH, Stein L, Xie H, Orkin SH, Armstrong SA
Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):5028-33.

An Unusual Case of Congenital Primitive Neuroectodermal Tumor With Ocular Metastasis.

Salgado C, Neff T*, Frazier L, Vargas SO, Vanderveen D. (Case report)
J Pediatr Hematol Oncol. 2012 Mar;34(2):e69-71.*corresponding author

Long-term polyclonal and multilineage engraftment of methylguanine methyltransferase P140K gene-modified dog hematopoietic cells in primary and secondary recipients.

Beard BC, Sud R, Keyser KA, Ironside C, Neff T, Gerull S, Trobridge GD, Kiem HP
Blood. 2009 May 21;113(21):5094-103.

Hematopoietic stem cell engraftment: a direct comparison between intramarrow and intravenous injection in nonhuman primates.

Jung CW, Beard BC, Morris JC, Neff T, Beebe K, Storer BE, Kiem HP
Exp Hematol. 2007 Jul;35(7):1132-9.

In vivo selection and chemoprotection after drug resistance gene therapy in a nonmyeloablative allogeneic transplantation setting in dogs.

Gerull S, Beard BC, Peterson LJ, Neff T, Kiem HP
Hum Gene Ther. 2007 May;18(5):451-6.

Improved short-term engraftment of lentivirally versus gammaretrovirally transduced allogeneic canine repopulating cells.

Neff T, Gerull S, Peterson LJ, Kiem HP
J Gene Med. 2007 May;9(5):357-61.

Polyclonal chemoprotection against temozolomide in a large-animal model of drug resistance gene therapy.

Neff T, Beard BC, Peterson LJ, Anandakumar P, Thompson J, Kiem HP
Blood. 2005 Feb 1;105(3):997-1002.

Efficient lentiviral gene transfer to canine repopulating cells using an overnight transduction protocol.

Horn PA, Keyser KA, Peterson LJ, Neff T, Thomasson BM, Thompson J, Kiem HP
Blood. 2004 May 15;103(10):3710-6.

Efficient gene transfer to hematopoietic repopulating cells using concentrated RD114-pseudotype vectors produced by human packaging cells.

Neff T, Peterson LJ, Morris JC, Thompson J, Zhang X, Horn PA, Thomasson BM, Kiem HP
Mol Ther. 2004 Feb;9(2):157-9.

Methylguanine methyltransferase-mediated in vivo selection and chemoprotection of allogeneic stem cells in a large-animal model.

Neff T, Horn PA, Peterson LJ, Thomasson BM, Thompson J, Williams DA, Schmidt M, Georges GE, von Kalle C, Kiem HP
J Clin Invest. 2003 Nov;112(10):1581-8.

Pharmacologically regulated in vivo selection in a large animal.

Neff T, Horn PA, Valli VE, Gown AM, Wardwell S, Wood BL, von Kalle C, Schmidt M, Peterson LJ, Morris JC, Richard RE, Clackson T, Kiem HP, Blau CA
Blood. 2002 Sep 15;100: 2026-2031.

Receptor specificity in the self renewal and differentiation of primary multipotential hemopoietic cells.

Zeng H, Jin L, Richard RE, Neff T, Otto KG, Thomis D, Miller AD, Blau CA
Blood. 2001 Jul 15;98(2):328-34.

Marrow sensitization to 5-fluorouracil using the ligands for Flt-3 and c-Kit.

Jin L, Neff T, Blau CA
Exp Hematol. 1999 Mar 27(3):520-5.

Cytokine prestimulation as a gene therapy strategy: implications for using the MDR1 gene as a dominant selectable marker.

Blau CA, Neff T, Papayannopoulou T
Blood. 1997 Jan 1;89(1):146-54.

The hematological effects of folate analogs: implications for using the dihydrofolate reductase gene for in vivo selection.

Blau CA, Neff T, Papayannopoulou T
Hum Gene Ther. 1996 Nov 10;7(17):2069-78.

Forced expression of cytidine deaminase confers resistance to cytosine arabinoside and gemcitabine.

Neff T, Blau CA
Exp Hematol. 1996 Sep;24(11):1340-6.


Histone Profiles in Cancer. 

Riedel SS, Neff T, Bernt KM.
Pharmacol Ther. 2015 Oct;154:87-109. doi: 10.1016/j.pharmthera.2015.07.004. Epub 2015 Jul 22.

Epigenetic modifiers in normal and malignant hematopoiesis. 

Haladyna JN, Yamauchi T, Neff T, Bernt KM
Epigenomics. 2015;7(2):301-20. doi: 10.2217/epi.14.88. Review.

Recent progress toward epigenetic therapies: the example of mixed lineage leukemia.

Neff T, Armstrong SA
Blood. 2013 Jun 13;121(24):4847-53. doi: 10.1182/blood-2013-02-474833. Epub 2013 May 6. Review.

Chromatin maps, histone modifications and leukemia.

Neff T, Armstrong SA
Leukemia. 2009 Jul;23(7):1243-51. Review.

Survival of the fittest: In vivo selection and stem cell gene therapy. Review.

Neff T, Beard BC, Kiem HP
Blood. 2006 Mar 1;107(5):1751-60.

Stem cell gene transfer-efficacy and safety in large animal studies. Review.

Horn PA, Morris JC, Neff T, Kiem HP
Mol Ther. 2004 Sep;10(3):417-31.

Pharmacologically regulated cell therapy. Review.

Neff, T and Blau, CA
Blood. 2001 May 1;97(9):2535-40.

Stem cell gene therapy, position effects and chromatin insulators. Review.

Neff T, Shotkoski F, Stamatoyannopoulos G
Stem Cells. 1997;15 Suppl 1:265-71.


1995-1996 “Cytidine-Deaminase as a Selectable Marker for Gene Therapy.”

University of Washington, Seattle, WA and Prof. Bernhard Kornhuber, Goethe University, Frankfurt a.M.
summa cum laude – (11/1999)