T cell acute lymphoblastic leukemia/lymphoma: A human cancer commonly associated with aberrant NOTCH1 signaling

Current Opinion in Hematology

Volumn 11, Issue 6, 2004, Pages 426-433

  Pear, Warren S ^a   Aster, Jon C ^b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

NOTCH signaling; T cell acute lymphoblastic leukemia lymphoma

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; COMPLEMENTARY DNA; GAMMA SECRETASE; GAMMA SECRETASE INHIBITOR; NOTCH RECEPTOR; NOTCH1 RECEPTOR;

ACUTE LYMPHOBLASTIC LEUKEMIA; ALZHEIMER DISEASE; BLOOD TOXICITY; CANCER GROWTH; CELL DIFFERENTIATION; CELL LINEAGE; CELL MATURATION; CELL SURVIVAL; CHROMOSOME TRANSLOCATION 7; EPITHELIUM CELL; GENE DELETION; GENE FUNCTION; GENE INSERTION; GENE MUTATION; GENE STRUCTURE; HEMATOPOIETIC STEM CELL; HUMAN; LEUKEMIA CELL LINE; LYMPHOMA CELL LINE; NONHUMAN; PATHOGENESIS; POINT MUTATION; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN MODIFICATION; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION; STEM CELL; T CELL LEUKEMIA; T CELL LYMPHOMA; TRANSCRIPTION INITIATION; TRANSGENE; TUMOR CELL;

AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ASPARTIC ENDOPEPTIDASES; ENDOPEPTIDASES; GENE EXPRESSION REGULATION, LEUKEMIC; HUMANS; LEUKEMIA, T-CELL, ACUTE; MUTATION; NEOPLASM PROTEINS; RECEPTOR, NOTCH1; RECEPTORS, CELL SURFACE; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS;

EID: 8544262178     PISSN: 10656251     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.moh.0000143965.90813.70     Document Type: Review

References (76)

1. Ellisen LW, Bird J, West DC, et al.: TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell 1991, 66:649-661.
2. Radtke F, Wilson A, Mancini SJ, et al: Notch regulation of lymphocyte development and function. Nat Immunol 2004, 5:247-253. A timely detailed review of the role of notch in murine lymphocyte development that focuses on data obtained from knockout mice.
3. Pear WS, Aster JC, Scott ML, et al.: Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles. J Exp Med 1996, 183:2283-2291.
4. Weng AP, Ferrando AA, Lee W, et al.: Activating mutations of NOTCH1 occur frequently in human T cell acute lymphoblastic leukemia. Science 2004, in press. This paper reports the discovery of frequent gain-of-function NOTCH1 mutations in human T cell acute lymphoblastic leukemia, including rather novel synergistic dual mutations involving the heterodimerization and PEST domains of the receptor. These findings expand the known role of NOTCH1 signals in human cancer and offers new therapeutic possibilities with γ-secretase inhibitors.
5. Bray S: Notch signalling in Drosophila: three ways to use a pathway. Semin Cell Dev Biol 1998, 9:591-597.
6. Schweisguth F: Notch signaling activity. Curr Biol 2004, 14:R129-R138. An excellent recent review focused on recent advances in understanding Notch signaling.
7. Fortini ME: Gamma-secretase-mediated proteolysis in cell-surface-receptor signalling. Nat Rev Mol Cell Biol 2002, 3:673-684.
8. Logeal F, Bessia C, Brou C, et al.: The Notch1 receptor is cleaved constitutively by a furin-like convertase. Proc Natl Acad Sci USA 1998, 95:8108-8112.
9. Sanchez-Irizarry C, Carpenter AC, Weng AP, et al.: Notch subunit heterodimerization and prevention of ligand-independent proteolytic activation depend respectively on a novel domain and the LNR repeats. Mol Cell Biol 2004, in press. Using a biochemical approach with recombinant NOTCH minireceptors, the authors define a minimal region required for stable association of NOTCH receptor subunits. These findings directed the search for the mutations in human T cell acute lymphoblastic leukemia described in [4]
10. Kurooka H, Kuroda K, Honjo T: Roles of the ankyrin repeats and C-terminal region of the mouse notch1 intracellular region. Nucleic Acids Res 1998, 26:5448-5455.
11. Kurooka H, Honjo T: Functional interaction between the mouse notch1 intracellular region and histone acetyltransferases PCAF and GCN5. J Biol Chem 2000, 275:17211-17220.
12. Brou C, Logeat F, Gupta N, et al.: A novel proteolytic cleavage involved in Notch signaling; the role of the disintegrin-metalloprotease TACE. Mol Cell 2000, 5:207-216.
13. Gupta-Rossi N, Six E, LeBail O, et al.: Monoubiquitination and endocytosis direct gamma-secretase cleavage of activated Notch receptor. J Cell Biol 2004, 166:73-83. An interesting set of studies conducted with cultured cells indicating that N™*, a NOTCH1 signaling intermediate, is subject to mono-ubiquitination on a conserved lysine residue just internal to the transmembrane domain. This modification, which may be needed for efficient endocytosis and further processing, represents another enzymatic step in NOTCH activation that could be amenable to pharmacologic intervention.
14. Hsieh JJ, Henkel T, Salmon P, et al.: Truncated mammalian Notch1 activates CBF1/RBPJk-repressed genes by a mechanism resembling that of Epstein-Barr virus EBNA2. Mol Cell Biol 1996, 16:952-959.
15. Schweisguth F, Posakony JW: Suppressor of Hairless, the Drosophila homolog of the mouse recombination signal-binding protein gene, controls sensory organ cell fates. Cell 1992, 69:1199-1212.
16. Christensen S, Kodoyianni V, Bosenberg M, et al.: lag-1, a gene required for lin-12 and glp-1 signaling in Caenorhabditis elegans, is homologous to human CBF1 and Drosophila Su(H). Development 1996, 122:1373-1383.
17. Hamaguchi Y, Mastunami N, Yamamoto Y, et al.: Cloning and characterization of a protein binding to the J kappa recombination signal sequence of immunoglobulin genes. Adv Exp Med Biol 1991, 292:177-186.
18. Kovall RA, Hendrickson WA: Crystal structure of the nuclear effector of Notch signaling, CSL, bound to DNA. Embo J 2004; epublished. The first high-resolution structure of the downstream mediator of canonical NOTCH signaling, this work shows that CSL has two rel homology domains and a β-strand-rich trefoil domain.
19. Wu L, Sun T, Kobayashi K, et al.: Identification of a family of mastermind-like transcriptional coactivators for mammalian notch receptors. Mol Cell Biol 2002, 22:7688-7700.
20. Fryer CJ, Lamar E, Turbachova I, et al.: Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex. Genes Dev 2002, 16:1397-1411.
21. Wallberg AE, Pedersen K, Lendahl U, et al.: p300 and PCAF act cooperatively to mediate transcriptional activation from chromatin templates by notch intracellular domains in vitro. Mol Cell Biol 2002, 22:7812-7819.
22. Jeffries S, Robbins DJ, Capobianco AJ: Characterization of a high-molecular-weight Notch complex in the nucleus of Notch(ic)-transformed RKE cells and in a human T-cell leukemia cell line. Mol Cell Biol 2002, 22:3927-3941.
23. Gupta-Rossi N, Le Bail O, Gonen H, et al.: Functional interaction between SEL-10, an F-box protein, and the nuclear form of activated Notch1 receptor. J Biol Chem 2001, 276:34371-34378.
24. Wu G, Lyapina S, Das I, et al.: SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin-mediated protein degradation. Mol Cell Biol 2001, 21:7403-7415.
25. Oberg C, Li J, Pauley A, et al.: The Notch intracellular domain is ubiquitinated and negatively regulated by the mammalian Sel-10 homolog. J Biol Chem 2001, 276:35847-35853.
26. Martinez Arias A, Zecchini V, Brennan K: CSL-independent Notch signalling: a checkpoint in cell fate decisions during development? Curr Opin Genet Dev 2002, 12:524-533.
27. Bush G, diSibio G, Miyamoto A, et al.: Ligand-induced signaling in the absence of furin processing of Notch1. Dev Biol 2001, 229:494-502.
28. Radtke F, Wilson A, MacDonald HR: Notch signaling in T- and B-cell development. Curr Opin Immunol 2004, 16:174-179.
29. Reizis B, Leder P: Direct induction of T lymphocyte-specific gene expression by the mammalian Notch signaling pathway. Genes Dev 2002,16:295-300.
30. Wolfer A, Wilson A, Nemir M, et al.: Inactivation of Notch1 impairs VDJbeta rearrangement and allows pre-TCR-independent survival of early alpha beta lineage thymocytes. Immunity 2002, 16:869-879.
31. Tanigaki K, Tsuji M, Yamamoto N, et al.: Regulation of alphabeta/gammadelta T cell lineage commitment and peripheral T cell responses by Notch/RBP-J signaling. Immunity 2004, 20:611-622. A study of the effects of conditional CSL knockout in Cre-Lck and Cre-CD4 mice, this paper supports a specific role for notch signals in αβ T cell development (versus γδ), but not in the CD4 versus CD8 cell fate choice. The paper provides fairly definitive evidence that notch signaling is not require for the CD4 versus CD8 cell choice, which has been a matter of controversy.
32. + stage of differentiation. Thus, although notch1 may function in establishing the pre-TCR, it seems to also have additional essential pre-TCR-independent functions.
33. Hadland BK, Manley NR, Su D, et al.: Gamma-secretase inhibitors repress thymocyte development. Proc Natl Acad Sci USA 2001, 98:7487-7491.
34. Doerfler P, Shearman MS, Perlmutter RM: Presenilin-dependent gamma-secretase activity modulates thymocyte development. Proc Natl Acad Sci USA 2001, 98:9312-9317.
35. Maillard I, Weng AP, Carpenter AC, et al.: Mastermind critically regulates Notch-mediated lymphoid cell fate decisions. Blood 2004; epublished. The authors demonstrate that retroviruses encoding a dominant negative form of human Mastermind-like-1 phenocopy the effects of conditional notch1 and notch2 inactivation on early T cell and marginal zone B cell development, respectively.
36. Pui JC, Allman D, Xu L, et al.: Notch1 expression in early lymphopoiesis influences B versus T lineage determination. Immunity 1999, 11:299-308.
37. Schmitt TM, de Pooler RF, Gronski MA, et al.: Induction of T cell development and establishment of T cell competence from embryonic stem cells differentiated in vitro. Nat Immunol 2004, 5:410-417. The authors show that OP9 bone marrow feeder cells expressing the notch ligand delta-like-1 can support T cell development from hematopoietic or embryonic stem cells. This promises to be a very powerful ex vivo system for studying the role of various signals in T cell development, including notch [32].
38. Hasserjian RP, Aster JC, Davi F, et al.: Modulated expression of notch1 during thymocyte development. Blood 1996, 88:970-976.
39. + stage of T cell development
40. Wolfer A, Bakker T, Wilson A, et al.: Inactivation of Notch 1 in immature thymocytes does not perturb CD4 or CD8T cell development. Nat Immunol 2001, 2:235-241.
41. Hoyne GF, Dallman MJ, Champion BR, et al.: Notch signalling in the regulation of peripheral immunity. Immunol Rev 2001, 182:215-227.
42. Eagar TN, Tang Q, Wolfe M, et al.: Notch 1 signaling regulates peripheral T cell activation. Immunity 2004, 20:407-415.
43. Aster J, Pear W, Hasserjian R, et al.: Functional analysis of the TAN-1 gene, a human homolog of Drosophila notch. Cold Spring Harb Symp Quant Biol 1994, 59:125-136.
44. Weng AP, Nam Y, Wolfe MS, et al.: Growth suppression of pre-T acute lymphoblastic leukemia cells by inhibition of notch signaling. Mol Cell Biol 2003, 23:655-664. This represents the first demonstration of a role for NOTCH1 signals in maintaining the growth of established human and murine T cell acute lymphoblastic leukemias.
45. Das I, Craig C, Funahashi Y, et al.: Notch oncoproteins depend on {gamma}-secretase/presenilin activity for processing and function. J Biol Chem 2004, 279:30771-30780.
46. Aster JC, Xu L, Karnell FG, et al.: Essential roles for ankyrin repeat and transactivation in induction of T-cell leukemia by notch1. Mol Cell Biol 2000, 20:7505-7515.
47. Feldman BJ, Hampton T, Cleary ML: A carboxy-terminal deletion mutant of Notch1 accelerates lymphoid oncogenesis in E2A-PBX1 transgenic mice. Blood 2000, 96:1906-1913.
48. Hoemann CD, Beaulieu N, Girard L, et al.: Two distinct Notch1 mutant alleles are involved in the induction of T-cell leukemia in c-myc transgenic mice. Mol Cell Biol 2000, 20:3831-3842.
49. Ferrando AA, Neuberg DS, Staunton J, et al.: Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell 2002, 1:75-87.
50. Hubbard EJ, Wu G, Kitajewski J, et al.: sel-10, a negative regulator of lin-12 activity in Caenorhabditis elegans, encodes a member of the CDC4 family of proteins. Genes Dev 1997, 11:3182-3193.
51. Tetzlaff MT, Yu W, Li M, et al.: Defective cardiovascular development and elevated cyclin E and Notch proteins in mice lacking the Fbw7 F-box protein. Proc Natl Acad Sci USA 2004, 101:3338-3345. Together with [52], this paper provides further evidence of the importance of proteins of the SEL-10/fbw7 family in negative regulation of nuclear notch activity.
52. Tsunematsu R, Nakayama K, Oike Y, et al.: Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular development. J Biol Chem 2004, 279:9417-9423. See [51].
53. Rebay I, Fehon RG, Artavanis-Tsakonas S: Specific truncations of Drosophila Notch define dominant activated and dominant negative forms of the receptor. Cell 1993, 74:319-329.
54. Kramer H: RIPping notch apart: a new role for endocytosis in signal transduction? Sci STKE 2000;2000:PE1.
55. Rand MD, Grimm LM, Artavanis-Tsakonas S, et al.: Calcium depletion dissociates and activates heterodimeric notch receptors. Mol Cell Biol 2000, 20:1825-1835.
56. Deftos ML, He YW, Ojala EW, et al.: Correlating notch signaling with thymocyte maturation. Immunity 1998, 9:777-786.
57. Beverly LJ, Capobianco AJ: Perturbation of Ikaros isoform selection by MLV integration is a cooperative event in Notch(IC)-induced T cell leukemogenesis. Cancer Cell 2003, 3:551-564. This paper suggests the existence of competition for promoter binding sites between ikaros and the notch signal mediator CSL, which could be functionally important in T cell development as well as T cell neoplasms.
58. Allman D, Karnell FG, Punt JA, et al.: Separation of Notch1 promoted lineage commitment and expansion/transformation in developing T cells. J Exp Med 2001, 194:99-106.
59. Bellavia D, Campese AF, Alesse E, et al.: Constitutive activation of NF-kappaB and T-cell leukemia/lymphoma in Notch3 transgenic mice. EMBO J 2000, 19:3337-3348.
60. + T cell development) in the Induction of T cell acute lymphoblastic leukemia by activated forms of notch1.
61. Tsuji H, Ishii-Ohba H, Ukai H, et al.: Radiation-induced deletions in the 5′ end region of Notch1 lead to the formation of truncated proteins and are involved in the development of mouse thymic lymphomas. Carcinogenesis 2003, 24:1257-1268. The authors identify a series of SCID T-ALL cell lines that express abnormal splice variants encoding constitutive active forms of notch1. This is the first example of an acquired abnormality of notch1 in murine T-ALL, and it documents an unusual mechanism for oncogene activation.
62. Kang-Decker N, Tong C, Boussouar F, et al.: Loss of CBP causes T cell lymphomagenesis in synergy with p27Kip1 insufficiency. Cancer Cell 2004, 5:177-189. This paper describes a novel model for T-ALL development, in which notch1 is highly expressed.
63. Rohn JL, Lauring AS, Linenberger ML, et al.: Transduction of Notch2 in feline leukemia virus-induced thymic lymphoma. J Virol 1996, 70:8071-8080.
64. Yan XQ, Sarmiento U, Sun Y, et al.: A novel Notch ligand, DII4, induces T-cell leukemia/lymphoma when overexpressed in mice by retroviral-mediated gene transfer. Blood 2001, 98:3793-3799.
65. Talora C, Campese AF, Bellavia D, et al.: Pre-TCR-triggered ERK signalling-dependent downregulation of E2A activity in Notch3-induced T-cell lymphoma. EMBO Rep 2003, 4:1067-1072. This paper suggests that a notch3-pre-TCR-id1 signaling axis contributes to the downregulation of e2a and T-ALL development in a murine model.
66. Haines N, Irvine KD: Glycosylation regulates Notch signalling. Nat Rev Mol Cell Biol 2003, 4:786-797.
67. Itoh M, Kim CH, Palardy G, et al.: Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta. Dev Cell 2003, 4:67-82.
68. Espinosa L, Ingles-Esteve J, Aguilera C, et al.: Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways. J Biol Chem 2003, 278:32227-32235.
69. Raya A, Kawakami Y, Rodriguez-Esteban C, et al.: Notch activity acts as a sensor for extracellular calcium during vertebrate left-right determination. Nature 2004, 427:121-128. This paper proposes a novel mechanism for left-right determination involving a calcium gradient that differentially affects notch function, presumably because of the relatively low calcium affinity of particular EGF and LNR repeats within the extracellular subunits of notch receptors.
70. Selkoe D, Kopan R: Notch and Presenilin: regulated intramembrane proteolysis links development and degeneration. Annu Rev Neurosci 2003, 26:565-597. An excellent review of the possible links between notch, γ-secretase, various developmental processes, and Alzheimer disease.
71. Kopan R, Ilagan MXG: Gamma-secretase: proteosome of the membrane? Nat Rev Mol Cell Biol 2004, 5:499-504. This review gives a concise overview of the functional significance of intramembranous proteolysis mediated by γ-secretase.
72. Donoviel DB, Hadjantonakis AK, Ikeda M, et al.: Mice lacking both presenilin genes exhibit early embryonic patterning defects. Genes Dev 1999, 13:2801-2810.
73. Geling A, Steiner H, Willem M, et al.: A gamma-secretase inhibitor blocks Notch signaling in vivo and causes a severe neurogenic phenotype in zebrafish. EMBO Rep 2002, 3:688-694.
74. Micchelli CA, Esler WP, Kimberly WT, et al.: Gamma-secretase/presenilin inhibitors for Alzheimer's disease phenocopy Notch mutations in Drosophila. FASEB J 2003, 17:79-81. Additional evidence that γ-secretase inhibitors predominantly induce effects that mimic notch loss of function, in the very well characterized fly developmental system.
75. Wong GT, Manfra D, Poulet FM, et al.: Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J Biol Chem 2004, 279:12876-12882. The first paper documenting the effects in mice of long-term oral administration of γ-secretase inhibitors. The major toxicities, a blockade of T cell development and aberrant differentiation of gut epithelial cells, are both likely attributable for notch inhibition.
76. Marjaux E, Hartmann D, De Strooper B: Presenilins in memory, Alzheimer's disease, and therapy. Neuron 2004, 42:189-192. A thoughtful discussion of the possible short-term and long-term complications of Notch signaling pathway blockade.