SCL, LMO1 and Notch1 Reprogram Thymocytes into Self-Renewing Cells

PLoS Genetics

Volumn 10, Issue 12, 2014, Pages

  Gerby, Bastien ^a,b   Tremblay, Cedric S ^a,b,e   Tremblay, Mathieu ^a,b   Rojas Sutterlin, Shanti ^a,b   Herblot, Sabine ^a,f   Hébert, Josée ^a,b,c   Sauvageau, Guy ^a,b,c   Lemieux, Sébastien ^a,b   Lécuyer, Eric ^b,d   Veiga, Diogo F T ^a,b   Hoang, Trang ^a,b  

^a INSTITUTE FOR RESEARCH IN IMMUNOLOGY AND CANCER   (Canada)

^b UNIVERSITÉ DE MONTRÉAL   (Canada)

^c MAISONNEUVE ROSEMONT HOSPITAL   (Canada)

^d CLIN RESEARCH INSTITUTE OF MONTREAL   (Canada)

^e MONASH UNIVERSITY   (Australia)

^f UNIVERSITY OF MONTREAL   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

LMO1 PROTEIN; LYL1 PROTEIN; MYC PROTEIN; NOTCH1 RECEPTOR; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR E2A; TRANSCRIPTION FACTOR HES 1; TRANSCRIPTION FACTOR TAL1; UNCLASSIFIED DRUG; BASIC HELIX LOOP HELIX TRANSCRIPTION FACTOR; LIM PROTEIN; LMO1 PROTEIN, MOUSE; LYL1 PROTEIN, MOUSE; NOTCH1 PROTEIN, MOUSE; NUCLEAR PROTEIN; ONCOPROTEIN; TAL1 PROTEIN, MOUSE; TUMOR PROTEIN;

ACUTE LYMPHOBLASTIC LEUKEMIA; ALLELE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL RENEWAL; CONTROLLED STUDY; DN3 THYMOCYTE; GAIN OF FUNCTION MUTATION; GENE OVEREXPRESSION; HUMAN; HUMAN CELL; LIFESPAN; LMO1 GENE; MOUSE; NONHUMAN; ONCOGENE; PRE LEUKEMIC STEM CELL; PROTEIN EXPRESSION; PROTEIN INTERACTION; SCL GENE; SIGNAL TRANSDUCTION; STEM CELL; T LYMPHOCYTE; T LYMPHOCYTE SUBPOPULATION; THYMOCYTE; TRANSCRIPTION INITIATION; AMINO ACID SEQUENCE; ANIMAL; CELL PROLIFERATION; CELL TRANSFORMATION; CYTOLOGY; DISEASE MODEL; GENE EXPRESSION REGULATION; GENE LOCUS; GENETICS; KNOCKOUT MOUSE; METABOLISM; MOLECULAR GENETICS; MUTATION; NUCLEAR REPROGRAMMING; PROMOTER REGION;

AMINO ACID SEQUENCE; ANIMALS; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; CELL PROLIFERATION; CELL TRANSFORMATION, NEOPLASTIC; CELLULAR REPROGRAMMING; DISEASE MODELS, ANIMAL; GENE EXPRESSION REGULATION, NEOPLASTIC; GENETIC LOCI; LIM DOMAIN PROTEINS; MICE; MICE, KNOCKOUT; MOLECULAR SEQUENCE DATA; MUTATION; NEOPLASM PROTEINS; NUCLEAR PROTEINS; PRECURSOR T-CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; PROMOTER REGIONS, GENETIC; PROTO-ONCOGENE PROTEINS; RECEPTOR, NOTCH1; THYMOCYTES; TRANSCRIPTION FACTORS; TRANSCRIPTIONAL ACTIVATION;

EID: 84919683992     PISSN: 15537390     EISSN: 15537404     Source Type: Journal    
DOI: 10.1371/journal.pgen.1004768     Document Type: Article

References (120)

1. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, et al. (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367: 645–648.
2. Valent P, Bonnet D, Wohrer S, Andreeff M, Copland M, et al. (2013) Heterogeneity of neoplastic stem cells: theoretical, functional, and clinical implications. Cancer Res 73: 1037–1045.
3. Bonnet D, Dick JE, (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3: 730–737.
4. Jordan CT, (2009) Cancer stem cells: controversial or just misunderstood? Cell Stem Cell 4: 203–205.
5. Vicente-Duenas C, Romero-Camarero I, Cobaleda C, Sanchez-Garcia I, (2013) Function of oncogenes in cancer development: a changing paradigm. EMBO J 32: 1502–1513.
6. Nguyen LV, Vanner R, Dirks P, Eaves CJ, (2012) Cancer stem cells: an evolving concept. Nat Rev Cancer 12: 133–143.
7. Greaves M, Maley CC, (2012) Clonal evolution in cancer. Nature 481: 306–313.
8. Krivtsov AV, Twomey D, Feng Z, Stubbs MC, Wang Y, et al. (2006) Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature 442: 818–822.
9. McCormack MP, Young LF, Vasudevan S, de Graaf CA, Codrington R, et al. (2010) The Lmo2 oncogene initiates leukemia in mice by inducing thymocyte self-renewal. Science 327: 879–883.
10. Hong D, Gupta R, Ancliff P, Atzberger A, Brown J, et al. (2008) Initiating and cancer-propagating cells in TEL-AML1-associated childhood leukemia. Science 319: 336–339.
11. Bhandoola A, Sambandam A, (2006) From stem cell to T cell: one route or many? Nat Rev Immunol 6: 117–126.
12. Martins VC, Ruggiero E, Schlenner SM, Madan V, Schmidt M, et al. (2012) Thymus-autonomous T cell development in the absence of progenitor import. J Exp Med 209: 1409–1417.
13. Zhang JA, Mortazavi A, Williams BA, Wold BJ, Rothenberg EV, (2012) Dynamic transformations of genome-wide epigenetic marking and transcriptional control establish T cell identity. Cell 149: 467–482.
14. Ciofani M, Schmitt TM, Ciofani A, Michie AM, Cuburu N, et al. (2004) Obligatory role for cooperative signaling by pre-TCR and Notch during thymocyte differentiation. J Immunol 172: 5230–5239.
15. Weng AP, Ferrando AA, Lee W, Morris JPt, Silverman LB, et al. (2004) Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 306: 269–271.
16. O'Neil J, Calvo J, McKenna K, Krishnamoorthy V, Aster JC, et al. (2006) Activating Notch1 mutations in mouse models of T-ALL. Blood 107: 781–785.
17. Tremblay M, Tremblay CS, Herblot S, Aplan PD, Hebert J, et al. (2010) Modeling T-cell acute lymphoblastic leukemia induced by the SCL and LMO1 oncogenes. Genes Dev 24: 1093–1105.
18. Bigas A, Espinosa L, (2012) Hematopoietic stem cells: to be or Notch to be. Blood 119: 3226–3235.
19. Koch U, Lehal R, Radtke F, (2013) Stem cells living with a Notch. Development 140: 689–704.
20. Chiang MY, Shestova O, Xu L, Aster JC, Pear WS (2012) Divergent effects of supraphysiological Notch signals on leukemia stem cells and hematopoietic stem cells. Blood.
21. Armstrong F, de la Grange PB, Gerby B, Rouyez MC, Calvo J, et al. (2009) NOTCH is a key regulator of human T-cell acute leukemia initiating cell activity. Blood 113: 1730–1740.
22. Gerby B, Clappier E, Armstrong F, Deswarte C, Calvo J, et al. (2011) Expression of CD34 and CD7 on human T-cell acute lymphoblastic leukemia discriminates functionally heterogeneous cell populations. Leukemia 25: 1249–1258.
23. Tatarek J, Cullion K, Ashworth T, Gerstein R, Aster JC, et al. (2011) Notch1 inhibition targets the leukemia-initiating cells in a Tal1/Lmo2 mouse model of T-ALL. Blood 118: 1579–1590.
24. Wendorff AA, Koch U, Wunderlich FT, Wirth S, Dubey C, et al. (2010) Hes1 is a critical but context-dependent mediator of canonical Notch signaling in lymphocyte development and transformation. Immunity 33: 671–684.
25. Dudley DD, Wang HC, Sun XH, (2009) Hes1 potentiates T cell lymphomagenesis by up-regulating a subset of notch target genes. PLoS One 4: e6678.
26. D'Altri T, Gonzalez J, Aifantis I, Espinosa L, Bigas A, (2011) Hes1 expression and CYLD repression are essential events downstream of Notch1 in T-cell leukemia. Cell Cycle 10: 1031–1036.
27. Weng AP, Millholland JM, Yashiro-Ohtani Y, Arcangeli ML, Lau A, et al. (2006) c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma. Genes Dev 20: 2096–2109.
28. Steininger A, Mobs M, Ullmann R, Kochert K, Kreher S, et al. (2011) Genomic loss of the putative tumor suppressor gene E2A in human lymphoma. J Exp Med 208: 1585–1593.
29. Palomero T, Lim WK, Odom DT, Sulis ML, Real PJ, et al. (2006) NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth. Proc Natl Acad Sci U S A 103: 18261–18266.
30. Chiang MY, Xu L, Shestova O, Histen G, L'Heureux S, et al. (2008) Leukemia-associated NOTCH1 alleles are weak tumor initiators but accelerate K-ras-initiated leukemia. J Clin Invest 118: 3181–3194.
31. Swiers G, Patient R, Loose M, (2006) Genetic regulatory networks programming hematopoietic stem cells and erythroid lineage specification. Dev Biol 294: 525–540.
32. Reynaud D, Ravet E, Titeux M, Mazurier F, Renia L, et al. (2005) SCL/TAL1 expression level regulates human hematopoietic stem cell self-renewal and engraftment. Blood 106: 2318–2328.
33. Lacombe J, Herblot S, Rojas-Sutterlin S, Haman A, Barakat S, et al. (2010) Scl regulates the quiescence and the long-term competence of hematopoietic stem cells. Blood 115: 792–803.
34. Souroullas GP, Salmon JM, Sablitzky F, Curtis DJ, Goodell MA, (2009) Adult hematopoietic stem and progenitor cells require either Lyl1 or Scl for survival. Cell Stem Cell 4: 180–186.
35. Porcher C, Swat W, Rockwell K, Fujiwara Y, Alt FW, et al. (1996) The T cell leukemia oncoprotein SCL/tal-1 is essential for development of all hematopoietic lineages. Cell 86: 47–57.
36. Schlaeger TM, Schuh A, Flitter S, Fisher A, Mikkola H, et al. (2004) Decoding hematopoietic specificity in the helix-loop-helix domain of the transcription factor SCL/Tal-1. Mol Cell Biol 24: 7491–7502.
37. Lecuyer E, Lariviere S, Sincennes MC, Haman A, Lahlil R, et al. (2007) Protein stability and transcription factor complex assembly determined by the SCL-LMO2 interaction. J Biol Chem 282: 33649–33658.
38. Ferrando AA, Neuberg DS, Staunton J, Loh ML, Huard C, et al. (2002) Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell 1: 75–87.
39. McGuire EA, Rintoul CE, Sclar GM, Korsmeyer SJ, (1992) Thymic overexpression of Ttg-1 in transgenic mice results in T-cell acute lymphoblastic leukemia/lymphoma. Mol Cell Biol 12: 4186–4196.
40. Aplan PD, Jones CA, Chervinsky DS, Zhao X, Ellsworth M, et al. (1997) An scl gene product lacking the transactivation domain induces bony abnormalities and cooperates with LMO1 to generate T-cell malignancies in transgenic mice. EMBO J 16: 2408–2419.
41. Larson RC, Lavenir I, Larson TA, Baer R, Warren AJ, et al. (1996) Protein dimerization between Lmo2 (Rbtn2) and Tal1 alters thymocyte development and potentiates T cell tumorigenesis in transgenic mice. Embo J 15: 1021–1027.
42. Hsu HL, Wadman I, Tsan JT, Baer R, (1994) Positive and negative transcriptional control by the TAL1 helix-loop-helix protein. Proc Natl Acad Sci U S A 91: 5947–5951.
43. Park ST, Sun XH, (1998) The Tal1 oncoprotein inhibits E47-mediated transcription. Mechanism of inhibition. J Biol Chem 273: 7030–7037.
44. Chervinsky DS, Zhao XF, Lam DH, Ellsworth M, Gross KW, et al. (1999) Disordered T-cell development and T-cell malignancies in SCL LMO1 double-transgenic mice: parallels with E2A-deficient mice. Mol Cell Biol 19: 5025–5035.
45. Yan W, Young AZ, Soares VC, Kelley R, Benezra R, et al. (1997) High incidence of T-cell tumors in E2A-null mice and E2A/Id1 double-knockout mice. Mol Cell Biol 17: 7317–7327.
46. Herblot S, Steff AM, Hugo P, Aplan PD, Hoang T, (2000) SCL and LMO1 alter thymocyte differentiation: inhibition of E2A-HEB function and pre-T alpha chain expression. Nat Immunol 1: 138–144.
47. O'Neil J, Shank J, Cusson N, Murre C, Kelliher M, (2004) TAL1/SCL induces leukemia by inhibiting the transcriptional activity of E47/HEB. Cancer Cell 5: 587–596.
48. Murre C, (2005) Helix-loop-helix proteins and lymphocyte development. Nat Immunol 6: 1079–1086.
49. Kee BL, (2009) E and ID proteins branch out. Nat Rev Immunol 9: 175–184.
50. Herblot S, Aplan PD, Hoang T, (2002) Gradient of E2A activity in B-cell development. Mol Cell Biol 22: 886–900.
51. Goardon N, Schuh A, Hajar I, Ma X, Jouault H, et al. (2002) Ectopic expression of TAL-1 protein in Ly-6E.1-htal-1 transgenic mice induces defects in B- and T-lymphoid differentiation. Blood 100: 491–500.
52. Robb L, Rasko JE, Bath ML, Strasser A, Begley CG, (1995) scl, a gene frequently activated in human T cell leukaemia, does not induce lymphomas in transgenic mice. Oncogene 10: 205–209.
53. Kelliher MA, Seldin DC, Leder P, (1996) Tal-1 induces T cell acute lymphoblastic leukemia accelerated by casein kinase IIalpha. Embo J 15: 5160–5166.
54. Aifantis I, Raetz E, Buonamici S, (2008) Molecular pathogenesis of T-cell leukaemia and lymphoma. Nat Rev Immunol 8: 380–390.
55. Kim D, Peng XC, Sun XH, (1999) Massive apoptosis of thymocytes in T-cell-deficient Id1 transgenic mice. Mol Cell Biol 19: 8240–8253.
56. Van Vlierberghe P, Ferrando A, (2012) The molecular basis of T cell acute lymphoblastic leukemia. J Clin Invest 122: 3398–3406.
57. Ono Y, Fukuhara N, Yoshie O, (1998) TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3. Mol Cell Biol 18: 6939–6950.
58. Lecuyer E, Herblot S, Saint-Denis M, Martin R, Begley CG, et al. (2002) The SCL complex regulates c-kit expression in hematopoietic cells through functional interaction with Sp1. Blood 100: 2430–2440.
59. Kusy S, Gerby B, Goardon N, Gault N, Ferri F, et al. (2010) NKX3.1 is a direct TAL1 target gene that mediates proliferation of TAL1-expressing human T cell acute lymphoblastic leukemia. J Exp Med 207: 2141–2156.
60. Sanda T, Lawton LN, Barrasa MI, Fan ZP, Kohlhammer H, et al. (2012) Core transcriptional regulatory circuit controlled by the TAL1 complex in human T cell acute lymphoblastic leukemia. Cancer Cell 22: 209–221.
61. McCormack MP, Shields BJ, Jackson JT, Nasa C, Shi W, et al. (2013) Requirement for Lyl1 in a model of Lmo2-driven early T-cell precursor ALL. Blood.
62. McMurray HR, Sampson ER, Compitello G, Kinsey C, Newman L, et al. (2008) Synergistic response to oncogenic mutations defines gene class critical to cancer phenotype. Nature 453: 1112–1116.
63. Ashton JM, Balys M, Neering SJ, Hassane DC, Cowley G, et al. (2012) Gene sets identified with oncogene cooperativity analysis regulate in vivo growth and survival of leukemia stem cells. Cell Stem Cell 11: 359–372.
64. Cancer Genome Atlas Research N (2013) Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 368: 2059–2074.
65. Kalender Atak Z, Gianfelici V, Hulselmans G, De Keersmaecker K, Devasia AG, et al. (2013) Comprehensive analysis of transcriptome variation uncovers known and novel driver events in T-cell acute lymphoblastic leukemia. PLoS Genet 9: e1003997.
66. Schmitt TM, Zuniga-Pflucker JC, (2002) Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in vitro. Immunity 17: 749–756.
67. Tan JB, Visan I, Yuan JS, Guidos CJ, (2005) Requirement for Notch1 signals at sequential early stages of intrathymic T cell development. Nat Immunol 6: 671–679.
68. Wang H, Zou J, Zhao B, Johannsen E, Ashworth T, et al. (2011) Genome-wide analysis reveals conserved and divergent features of Notch1/RBPJ binding in human and murine T-lymphoblastic leukemia cells. Proc Natl Acad Sci U S A 108: 14908–14913.
69. Aster JC, Pear WS, Blacklow SC, (2008) Notch signaling in leukemia. Annu Rev Pathol 3: 587–613.
70. Deneault E, Cellot S, Faubert A, Laverdure JP, Frechette M, et al. (2009) A functional screen to identify novel effectors of hematopoietic stem cell activity. Cell 137: 369–379.
71. Rossi L, Lin KK, Boles NC, Yang L, King KY, et al. (2012) Less is more: unveiling the functional core of hematopoietic stem cells through knockout mice. Cell Stem Cell 11: 302–317.
72. Sharma VM, Calvo JA, Draheim KM, Cunningham LA, Hermance N, et al. (2006) Notch1 contributes to mouse T-cell leukemia by directly inducing the expression of c-myc. Mol Cell Biol 26: 8022–8031.
73. Kunisato A, Chiba S, Nakagami-Yamaguchi E, Kumano K, Saito T, et al. (2003) HES-1 preserves purified hematopoietic stem cells ex vivo and accumulates side population cells in vivo. Blood 101: 1777–1783.
74. Hannah R, Joshi A, Wilson NK, Kinston S, Gottgens B, (2011) A compendium of genome-wide hematopoietic transcription factor maps supports the identification of gene regulatory control mechanisms. Exp Hematol 39: 531–541.
75. Wilson NK, Foster SD, Wang X, Knezevic K, Schutte J, et al. (2010) Combinatorial transcriptional control in blood stem/progenitor cells: genome-wide analysis of ten major transcriptional regulators. Cell Stem Cell 7: 532–544.
76. Lecuyer E, Hoang T, (2004) SCL: from the origin of hematopoiesis to stem cells and leukemia. Exp Hematol 32: 11–24.
77. Ikawa T, Kawamoto H, Goldrath AW, Murre C, (2006) E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment. J Exp Med 203: 1329–1342.
78. Miyazaki K, Miyazaki M, Murre C, (2014) The establishment of B versus T cell identity. Trends Immunol 35: 205–210.
79. Bain G, Quong MW, Soloff RS, Hedrick SM, Murre C, (1999) Thymocyte maturation is regulated by the activity of the helix-loop-helix protein, E47. J Exp Med 190: 1605–1616.
80. Zhuang Y, Cheng P, Weintraub H, (1996) B-lymphocyte development is regulated by the combined dosage of three basic helix-loop-helix genes, E2A, E2-2, and HEB. Mol Cell Biol 16: 2898–2905.
81. Deleuze V, El-Hajj R, Chalhoub E, Dohet C, Pinet V, et al. (2012) Angiopoietin-2 is a direct transcriptional target of TAL1, LYL1 and LMO2 in endothelial cells. PLoS One 7: e40484.
82. Zohren F, Souroullas GP, Luo M, Gerdemann U, Imperato MR, et al. (2012) The transcription factor Lyl-1 regulates lymphoid specification and the maintenance of early T lineage progenitors. Nat Immunol 13: 761–769.
83. Homminga I, Pieters R, Langerak AW, de Rooi JJ, Stubbs A, et al. (2011) Integrated transcript and genome analyses reveal NKX2-1 and MEF2C as potential oncogenes in T cell acute lymphoblastic leukemia. Cancer Cell 19: 484–497.
84. Smith S, Tripathi R, Goodings C, Cleveland S, Mathias E, et al. (2014) LIM Domain Only-2 (LMO2) Induces T-Cell Leukemia by Two Distinct Pathways. PLoS One 9: e85883.
85. Homminga I, Vuerhard MJ, Langerak AW, Buijs-Gladdines J, Pieters R, et al. (2012) Characterization of a pediatric T-cell acute lymphoblastic leukemia patient with simultaneous LYL1 and LMO2 rearrangements. Haematologica 97: 258–261.
86. Giambra V, Jenkins CR, Wang H, Lam SH, Shevchuk OO, et al. (2012) NOTCH1 promotes T cell leukemia-initiating activity by RUNX-mediated regulation of PKC-theta and reactive oxygen species. Nat Med 18: 1693–1698.
87. King B, Trimarchi T, Reavie L, Xu L, Mullenders J, et al. (2013) The ubiquitin ligase FBXW7 modulates leukemia-initiating cell activity by regulating MYC stability. Cell 153: 1552–1566.
88. Maillard I, Koch U, Dumortier A, Shestova O, Xu L, et al. (2008) Canonical notch signaling is dispensable for the maintenance of adult hematopoietic stem cells. Cell Stem Cell 2: 356–366.
89. Yuan JS, Kousis PC, Suliman S, Visan I, Guidos CJ, (2010) Functions of notch signaling in the immune system: consensus and controversies. Annu Rev Immunol 28: 343–365.
90. Phelan JD, Saba I, Zeng H, Kosan C, Messer MS, et al. (2013) Growth factor independent-1 maintains Notch1-dependent transcriptional programming of lymphoid precursors. PLoS Genet 9: e1003713.
91. Tzoneva G, Ferrando AA, (2012) Recent advances on NOTCH signaling in T-ALL. Curr Top Microbiol Immunol 360: 163–182.
92. De Obaldia ME, Bell JJ, Wang X, Harly C, Yashiro-Ohtani Y, et al. (2013) T cell development requires constraint of the myeloid regulator C/EBP-alpha by the Notch target and transcriptional repressor Hes1. Nat Immunol 14: 1277–1284.
93. Laurenti E, Varnum-Finney B, Wilson A, Ferrero I, Blanco-Bose WE, et al. (2008) Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity. Cell Stem Cell 3: 611–624.
94. Baena E, Ortiz M, Martinez AC, de Alboran IM, (2007) c-Myc is essential for hematopoietic stem cell differentiation and regulates Lin(-)Sca-1(+)c-Kit(-) cell generation through p21. Exp Hematol 35: 1333–1343.
95. Wilson A, Murphy MJ, Oskarsson T, Kaloulis K, Bettess MD, et al. (2004) c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation. Genes Dev 18: 2747–2763.
96. Reavie L, Della Gatta G, Crusio K, Aranda-Orgilles B, Buckley SM, et al. (2010) Regulation of hematopoietic stem cell differentiation by a single ubiquitin ligase-substrate complex. Nat Immunol 11: 207–215.
97. O'Neil J, Grim J, Strack P, Rao S, Tibbitts D, et al. (2007) FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors. J Exp Med 204: 1813–1824.
98. Nakagawa M, Takizawa N, Narita M, Ichisaka T, Yamanaka S, (2010) Promotion of direct reprogramming by transformation-deficient Myc. Proc Natl Acad Sci U S A 107: 14152–14157.
99. Roderick JE, Tesell J, Shultz LD, Brehm MA, Greiner DL, et al. (2014) c-Myc inhibition prevents leukemia initiation in mice and impairs the growth of relapsed and induction failure pediatric T-ALL cells. Blood 123: 1040–1050.
100. Loosveld M, Castellano R, Gon S, Goubard A, Crouzet T, et al. (2014) Therapeutic targeting of c-Myc in T-cell acute lymphoblastic leukemia, T-ALL. Oncotarget 5: 3168–3172.
101. Smith LJ, Curtis JE, Messner HA, Senn JS, Furthmayr H, et al. (1983) Lineage infidelity in acute leukemia. Blood 61: 1138–1145.
102. Ischenko I, Zhi J, Moll UM, Nemajerova A, Petrenko O, (2013) Direct reprogramming by oncogenic Ras and Myc. Proc Natl Acad Sci U S A 110: 3937–3942.
103. Chiu PP, Jiang H, Dick JE, (2010) Leukemia-initiating cells in human T-lymphoblastic leukemia exhibit glucocorticoid resistance. Blood 116: 5268–5279.
104. Soulier J, Clappier E, Cayuela JM, Regnault A, Garcia-Peydro M, et al. (2005) HOXA genes are included in genetic and biologic networks defining human acute T-cell leukemia (T-ALL). Blood 106: 274–286.
105. Simon C, Chagraoui J, Krosl J, Gendron P, Wilhelm B, et al. (2012) A key role for EZH2 and associated genes in mouse and human adult T-cell acute leukemia. Genes Dev 26: 651–656.
106. Nagel S, Venturini L, Meyer C, Kaufmann M, Scherr M, et al. (2010) Multiple mechanisms induce ectopic expression of LYL1 in subsets of T-ALL cell lines. Leuk Res 34: 521–528.
107. Zhuang Y, Kim CG, Bartelmez S, Cheng P, Groudine M, et al. (1992) Helix-loop-helix transcription factors E12 and E47 are not essential for skeletal or cardiac myogenesis, erythropoiesis, chondrogenesis, or neurogenesis. Proc Natl Acad Sci U S A 89: 12132–12136.
108. Malissen M, Gillet A, Ardouin L, Bouvier G, Trucy J, et al. (1995) Altered T cell development in mice with a targeted mutation of the CD3-epsilon gene. EMBO J 14: 4641–4653.
109. Zhumabekov T, Corbella P, Tolaini M, Kioussis D, (1995) Improved version of a human CD2 minigene based vector for T cell-specific expression in transgenic mice. J Immunol Methods 185: 133–140.
110. Greaves DR, Wilson FD, Lang G, Kioussis D, (1989) Human CD2 3'-flanking sequences confer high-level, T cell-specific, position-independent gene expression in transgenic mice. Cell 56: 979–986.
111. Harrison DE, Jordan CT, Zhong RK, Astle CM, (1993) Primitive hemopoietic stem cells: direct assay of most productive populations by competitive repopulation with simple binomial, correlation and covariance calculations. Exp Hematol 21: 206–219.
112. Ema H, Nakauchi H, (2000) Expansion of hematopoietic stem cells in the developing liver of a mouse embryo. Blood 95: 2284–2288.
113. Tanigawa T, Elwood N, Metcalf D, Cary D, DeLuca E, et al. (1993) The SCL gene product is regulated by and differentially regulates cytokine responses during myeloid leukemic cell differentiation. Proc Natl Acad Sci U S A 90: 7864–7868.
114. Trickett A, Kwan YL, (2003) T cell stimulation and expansion using anti-CD3/CD28 beads. J Immunol Methods 275: 251–255.
115. Gautier L, Cope L, Bolstad BM, Irizarry RA, (2004) affy—analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20: 307–315.
116. Breitling R, Armengaud P, Amtmann A, Herzyk P, (2004) Rank products: a simple, yet powerful, new method to detect differentially regulated genes in replicated microarray experiments. FEBS Lett 573: 83–92.
117. Salmon-Divon M, Dvinge H, Tammoja K, Bertone P, (2010) PeakAnalyzer: genome-wide annotation of chromatin binding and modification loci. BMC Bioinformatics 11: 415.
118. Tremblay M, Herblot S, Lecuyer E, Hoang T, (2003) Regulation of pT alpha gene expression by a dosage of E2A, HEB, and SCL. J Biol Chem 278: 12680–12687.
119. Lacombe J, Krosl G, Tremblay M, Gerby B, Martin R, et al. (2013) Genetic interaction between Kit and Scl. Blood 122: 1150–1161.
120. Lachmann A, Xu H, Krishnan J, Berger SI, Mazloom AR, et al. (2010) ChEA: transcription factor regulation inferred from integrating genome-wide ChIP-X experiments. Bioinformatics 26: 2438–2444.