Genome-scale expression and transcription factor binding profiles reveal therapeutic targets in transgenic ERG myeloid leukemia

Blood

Volumn 122, Issue 15, 2013, Pages 2694-2703

  Goldberg, Liat ^a,b   Tijssen, Marloes R ^c   Birger, Yehudit ^a   Hannah, Rebecca L ^c   Kinston, Sarah J ^c   Schütte, Judith ^c   Beck, Dominik ^d   Knezevic, Kathy ^d   Schiby, Ginette ^a   Jacob Hirsch, Jasmine ^a   Biran, Anat ^b   Kloog, Yoel ^b   Marcucci, Guido ^e   Bloomfield, Clara D ^e   Aplan, Peter D ^f   Pimanda, John E ^d   Göttgens, Berthold ^c   Izraeli, Shai ^a,b  

^a SHEBA MEDICAL CENTER   (Israel)

^b TEL AVIV UNIVERSITY   (Israel)

^c UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^d UNIVERSITY OF NEW SOUTH WALES   (Australia)

^e OHIO STATE UNIVERSITY   (United States)

^f NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOGLOBULIN G; PROTEIN KINASE PIM 1; TRANSCRIPTION FACTOR ERG; TRANSFORMING GROWTH FACTOR ALPHA; TRANSFORMING GROWTH FACTOR BETA1;

ACUTE GRANULOCYTIC LEUKEMIA; ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; CANCER GROWTH; CONTROLLED STUDY; ENHANCER REGION; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENOME ANALYSIS; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VITRO STUDY; IN VIVO STUDY; LEUKEMIA CELL; LEUKEMOGENESIS; MOUSE; MYELOID LEUKEMIA; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; UPREGULATION;

EID: 84888218254     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2013-01-477133     Document Type: Article

References (55)

1. Loughran SJ, Kruse EA, Hacking DF, et al. The transcription factor Erg is essential for definitive hematopoiesis and the function of adult hematopoietic stem cells. Nat Immunol. 2008;9(7):810-819.
2. Taoudi S, Bee T, Hilton A, et al. ERG dependence distinguishes developmental control of hematopoietic stem cell maintenance from hematopoietic specification. Genes Dev. 2011;25(3):251-262.
3. Wilson NK, Foster SD, Wang X, et al. Combinatorial transcriptional control in blood stem/progenitor cells: genome-wide analysis of ten major transcriptional regulators. Cell Stem Cell. 2010;7(4):532-544.
4. Giovannini M, Biegel JA, Serra M, et al. EWS-erg and EWS-Fli1 fusion transcripts in Ewing's sarcoma and primitive neuroectodermal tumors with variant translocations. J Clin Invest. 1994;94(2):489-496.
5. Kong XT, Ida K, Ichikawa H, et al. Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t (16;21) (p11;q22) and identification of a novel transcript. Blood. 1997;90(3):1192-1199.
6. Tomlins SA, Rhodes DR, Perner S, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005;310(5748):644- 648.
7. Salek-Ardakani S, Smooha G, de Boer J, et al. ERG is a megakaryocytic oncogene. Cancer Res. 2009;69(11):4665-4673.
8. Baldus CD, Burmeister T, Martus P, et al. High expression of the ETS transcription factor ERG predicts adverse outcome in acute T-lymphoblastic leukemia in adults. J Clin Oncol. 2006;24(29):4714-4720.
9. Marcucci G, Baldus CD, Ruppert AS, et al. Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute myeloid leukemia with normal karyotype: a Cancer and Leukemia Group B study. J Clin Oncol. 2005;23(36):9234-9242.
10. Metzeler KH, Dufour A, Benthaus T, et al. ERG expression is an independent prognostic factor and allows refined risk stratification in cytogenetically normal acute myeloid leukemia: a comprehensive analysis of ERG, MN1, and BAALC transcript levels using oligonucleotide microarrays. J Clin Oncol. 2009;27(30):5031-5038.
11. Eppert K, Takenaka K, Lechman ER, et al. Stem cell gene expression programs influence clinical outcome in human leukemia. Nat Med. 2011;17(9):1086-1093.
12. Thoms JA, Birger Y, Foster S, et al. ERG promotes T-acute lymphoblastic leukemia and is transcriptionally regulated in leukemic cells by a stem cell enhancer. Blood. 2011;117(26):7079-7089.
13. Li Z, Godinho FJ, Klusmann JH, Garriga-Canut M, Yu C, Orkin SH. Developmental stage-selective effect of somatically mutated leukemogenic transcription factor GATA1. Nat Genet. 2005;37(6):613-619.
14. Göttgens B, Nastos A, Kinston S, et al. Establishing the transcriptional programme for blood: the SCL stem cell enhancer is regulated by a multiprotein complex containing Ets and GATA factors. EMBO J. 2002;21(12):3039-3050.
15. Ishida Y, Levin J, Baker G, et al. Biological and biochemical characteristics of murine megakaryoblastic cell line L8057. Exp Hematol. 1993;21(2):289-298.
16. Göttgens B, McLaughlin F, Bockamp EO, et al. Transcription of the SCL gene in erythroid and CD34 positive primitive myeloid cells is controlled by a complex network of lineage-restricted chromatindependent and chromatin-independent regulatory elements. Oncogene. 1997;15(20):2419-2428.
17. Sánchez M, Göttgens B, Sinclair AM, et al. An SCL 39 enhancer targets developing endothelium together with embryonic and adult haematopoietic progenitors. Development. 1999;126(17):3891-3904.
18. Rotblat B, Ehrlich M, Haklai R, Kloog Y. The Ras inhibitor farnesylthiosalicylic acid (Salirasib) disrupts the spatiotemporal localization of active Ras: a potential treatment for cancer. Methods Enzymol. 2008;439:467-489.
19. Novershtern N, Subramanian A, Lawton LN, et al. Densely interconnected transcriptional circuits control cell states in human hematopoiesis. Cell. 2011;144(2):296-309.
20. Gentles AJ, Plevritis SK, Majeti R, Alizadeh AA. Association of a leukemic stem cell gene expression signature with clinical outcomes in acute myeloid leukemia. JAMA. 2010;304(24):2706-2715.
21. Diffner E, Beck D, Gudgin E, et al. Activity of a heptad of transcription factors is associated with stem cell programs and clinical outcome in acute myeloid leukemia. Blood. 2013;121(12):2289-2300.
22. Ng AP, Kauppi M, Metcalf D, DiRago L, Hyland CD, Alexander WS. Characterization of thrombopoietin (TPO)-responsive progenitor cells in adult mouse bone marrow with in vivo megakaryocyte and erythroid potential. Proc Natl Acad Sci USA. 2012;109(7):2364-2369.
23. Pronk CJ, Rossi DJ, Månsson R, et al. Elucidation of the phenotypic, functional, and molecular topography of a myeloerythroid progenitor cell hierarchy. Cell Stem Cell. 2007;1(4):428-442.
24. Rieger MA, Smejkal BM, Schroeder T. Improved prospective identification of megakaryocyteerythrocyte progenitor cells. Br J Haematol. 2009;144(3):448-451.
25. Donaldson IJ, Chapman M, Kinston S, et al. Genome-wide identification of cis-regulatory sequences controlling blood and endothelial development. Hum Mol Genet. 2005;14(5):595-601.
26. Oram SH, Thoms JA, Pridans C, et al. A previously unrecognized promoter of LMO2 forms part of a transcriptional regulatory circuit mediating LMO2 expression in a subset of T-acute lymphoblastic leukaemia patients. Oncogene. 2010;29(43):5796-5808.
27. Pimanda JE, Ottersbach K, Knezevic K, et al. Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development. Proc Natl Acad Sci USA. 2007;104(45):17692-17697.
28. McLean CY, Bristor D, Hiller M, et al. GREAT improves functional interpretation of cis-regulatory regions. Nat Biotechnol. 2010;28(5):495-501.
29. Dennis G Jr, Sherman BT, Hosack DA, et al. DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 2003;4(5):P3.
30. Hahn CN, Chong CE, Carmichael CL, et al. Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia. Nat Genet. 2011;43(10):1012-1017.
31. Luesink M, Hollink IH, van der Velden VH, et al. High GATA2 expression is a poor prognostic marker in pediatric acute myeloid leukemia. Blood. 2012;120(10):2064-2075.
32. Tsai FY, Orkin SH. Transcription factor GATA-2 is required for proliferation/survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation. Blood. 1997;89(10):3636-3643.
33. Rowlinson JM, Gering M. Hey2 acts upstream of Notch in hematopoietic stem cell specification in zebrafish embryos. Blood. 2010;116(12):2046-2056.
34. Gale NW, Kaplan S, Lowenstein EJ, Schlessinger J, Bar-Sagi D. Grb2 mediates the EGF-dependent activation of guanine nucleotide exchange on Ras. Nature. 1993;363(6424):88-92.
35. Radich JP, Kopecky KJ, Willman CL, et al. N-ras mutations in adult de novo acute myelogenous leukemia: prevalence and clinical significance. Blood. 1990;76(4):801-807.
36. Goldberg L, Israeli R, Kloog Y. FTS and 2-DG induce pancreatic cancer cell death and tumor shrinkage in mice. Cell Death Dis. 2012;3:e284.
37. Goldberg L, Kloog Y. A Ras inhibitor tilts the balance between Rac and Rho and blocks phosphatidylinositol 3-kinase-dependent glioblastoma cell migration. Cancer Res. 2006;66(24):11709-11717.
38. Bustinza-Linares E, Kurzrock R, Tsimberidou AM. Salirasib in the treatment of pancreatic cancer. Future Oncol. 2010;6(6):885-891.
39. Brault L, Gasser C, Bracher F, Huber K, Knapp S, Schwaller J. PIM serine/threonine kinases in the pathogenesis and therapy of hematologic malignancies and solid cancers. Haematologica. 2010;95(6):1004-1015.
40. Magistroni V, Mologni L, Sanselicio S, et al. ERG deregulation induces PIM1 over-expression and aneuploidy in prostate epithelial cells. PLoS ONE. 2011;6(11):e28162.
41. Eichmann A, Yuan L, Bréant C, Alitalo K, Koskinen PJ. Developmental expression of pim kinases suggests functions also outside of the hematopoietic system. Oncogene. 2000;19(9):1215-1224.
42. Batra V, Maris JM, Kang MH, et al. Initial testing (stage 1) of SGI-1776, a PIM1 kinase inhibitor, by the pediatric preclinical testing program. Pediatr Blood Cancer. 2012;59(4):749-752.
43. Chen LS, Redkar S, Taverna P, Cortes JE, Gandhi V. Mechanisms of cytotoxicity to Pim kinase inhibitor, SGI-1776, in acute myeloid leukemia. Blood. 2011;118(3):693-702.
44. de Jonge HJ, Valk PJ, Veeger NJ, et al. High VEGFC expression is associated with unique gene expression profiles and predicts adverse prognosis in pediatric and adult acute myeloid leukemia. Blood. 2010;116(10):1747-1754.
45. Carmichael CL, Metcalf D, Henley KJ, et al. Hematopoietic overexpression of the transcription factor Erg induces lymphoid and erythromegakaryocytic leukemia. Proc Natl Acad Sci USA. 2012;109(38):15437-15442.
46. Huang Z, Dore LC, Li Z, et al. GATA-2 reinforces megakaryocyte development in the absence of GATA-1. Mol Cell Biol. 2009;29(18):5168-5180.
47. Niessen K, Karsan A. Notch signaling in cardiac development. Circ Res. 2008;102(10):1169-1181.
48. Lin CY, Lovén J, Rahl PB, et al. Transcriptional amplification in tumor cells with elevated c-Myc. Cell. 2012;151(1):56-67.
49. Bester AC, Roniger M, Oren YS, et al. Nucleotide deficiency promotes genomic instability in early stages of cancer development. Cell. 2011;145(3):435-446.
50. Cuypers HT, Selten G, Quint W, et al. Murine leukemia virus-induced T-cell lymphomagenesis: integration of proviruses in a distinct chromosomal region. Cell. 1984;37(1):141-150.
51. Amson R, Sigaux F, Przedborski S, Flandrin G, Givol D, Telerman A. The human protooncogene product p33pim is expressed during fetal hematopoiesis and in diverse leukemias. Proc Natl Acad Sci USA. 1989;86(22):8857-8861.
52. Valdman A, Fang X, Pang ST, Ekman P, Egevad L. Pim-1 expression in prostatic intraepithelial neoplasia and human prostate cancer. Prostate. 2004;60(4):367-371.
53. Grundler R, Brault L, Gasser C, et al. Dissection of PIM serine/threonine kinases in FLT3-ITD-induced leukemogenesis reveals PIM1 as regulator of CXCL12-CXCR4-mediated homing and migration. J Exp Med. 2009;206(9):1957-1970.
54. Kim KT, Baird K, Ahn JY, et al. Pim-1 is upregulated by constitutively activated FLT3 and plays a role in FLT3-mediated cell survival. Blood. 2005;105(4):1759-1767.
55. Mumenthaler SM, Ng PY, Hodge A, et al. Pharmacologic inhibition of Pim kinases alters prostate cancer cell growth and resensitizes chemoresistant cells to taxanes. Mol Cancer Ther. 2009;8(10):2882-2893.