Activation of the T-Cell Oncogene LMO2 after Gene Therapy for X-Linked Severe Combined Immunodeficiency

New England Journal of Medicine

Volumn 350, Issue 9, 2004, Pages 913-922

  McCormack, Matthew P ^a   Rabbitts, Terence H ^b  

^a ROYAL MELBOURNE HOSPITAL   (Australia)

^b MRC LABORATORY OF MOLECULAR BIOLOGY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; CD8 ANTIGEN; GROWTH FACTOR; INTERLEUKIN 2 RECEPTOR; INTERLEUKIN 2 RECEPTOR GAMMA; RECEPTOR SUBUNIT; RETROVIRUS VECTOR; UNCLASSIFIED DRUG;

B LYMPHOCYTE; CELL MATURATION; CHROMOSOME TRANSLOCATION; CLINICAL TRIAL; COMBINED IMMUNODEFICIENCY; GENE ACTIVATION; GENE EXPRESSION; GENE TARGETING; GENETIC TRANSDUCTION; HEMATOPOIETIC STEM CELL; HUMAN; LEUKEMOGENESIS; LYMPHOCYTE CLONE; LYMPHOCYTE COUNT; LYMPHOCYTE DIFFERENTIATION; NATURAL KILLER CELL; NONHUMAN; ONCOGENE; ONCOGENE LMO2; OUTCOMES RESEARCH; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE; VIRAL GENE THERAPY; X CHROMOSOME LINKED DISORDER;

ANIMALS; DNA-BINDING PROTEINS; GENE EXPRESSION REGULATION; GENE EXPRESSION REGULATION, LEUKEMIC; GENE THERAPY; GENETIC DISEASES, X-LINKED; HUMANS; LEUKEMIA, T-CELL; METALLOPROTEINS; ONCOGENES; RECEPTORS, INTERLEUKIN-2; RETROVIRIDAE; SEVERE COMBINED IMMUNODEFICIENCY; T-LYMPHOCYTES; TRANSLOCATION, GENETIC; VIRUS ACTIVATION;

EID: 1342289322     PISSN: 00284793     EISSN: None     Source Type: Journal    
DOI: 10.1056/NEJMra032207     Document Type: Review

References (90)

1. Thomas CE, Ehrhardt A, Kay MA. Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genet 2003;4:346-58.
2. Hacein-Bey-Abina S, Le Deist F, Carlier F, et al. Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. N Engl J Med 2002;346:21185-93.
3. Kondo M, Weissman IL, Akashi K. Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 1997;91:2661-72.
4. Akashi K, Traver D, Kondo M, Weissman IL. Lymphoid development from hematopoietic stem cells. Int J Hematol 1999;69: 217-26.
5. Weissman IL, Anderson DJ, Gage F. Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations. Annu Rev Cell Dev Biol 2001; 17:387-403.
6. Miyamoto T, Iwasaki H, Reizis B, et al. Myeloid or lymphoid promiscuity as a critical step in hematopoietic lineage commitment. Dev Cell 2002;3:137-47.
7. Leonard WJ, Noguchi M, Russell SM. Sharing of a common gamma chain, gamma c, by the IL-2, IL-4, and IL-7 receptors: implications for X-linked severe combined immunodeficiency (XSCID). Adv Exp Med Biol 1994;365:225-32.
8. Hacein-Bey-Abina S, von Kalle C, Schmidt M, et al. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med 2003;348:255-6.
9. Hacein-Bey-Abina, S, von Kalle C, Schmidt M, et al. LMO2-associated clonal T cell proliferations in two patients after gene therapy for SCID-X1. Science 2003;302: 415-9.
10. Boehm T, Foroni L, Kaneko Y, Perutz MF, Rabbitts TH. The rhombotin family of cysteine-rich LIM-domain oncogenes: distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13. Proc Natl Acad Sci U S A 1991;88: 4367-71.
11. Royer-Pokora B, Loos U, Ludwig W-D. TrG-2, a new gene encoding a cysteine-rich protein with the LIM motif, is overexpressed in acute T-cell leukemia with the t(1l;14) (p13;q11). Oncogene 1991;6:1887-93.
12. Noguchi M, Yi H, Rosenblatt HM, et al. Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans. Cell 1993;73: 147-57.
13. Mikkers H, Berns A. Retroviral insertional mutagenesis: tagging cancer pathways. Adv Cancer Res 2003;88:53-99.
14. Cornetta K, Morgan RA, Anderson WF. Safety issues related to retroviral-mediated gene transfer in humans. Hum Gene Ther 1991;2:5-14.
15. Gray DA. Insertional mutagenesis: neoplasis arising from retroviral integration. Cancer Invest 1991;9:295-304.
16. Suzuki T, Shen H, Akagi K, et al. New genes involved in cancer identified by retroviral tagging. Nat Genet 2002;32:166-74. [Erratum, Nat Genet 2002;32:331.]
17. Suzuki T, Shen H, Akagi K, et al. New genes involved in cancer identified by retroviral tagging. Nat Genet 2002;32:166-74. [Erratum, Nat Genet 2002;32:331.
18. Kim R, Trubetskoy A, Suzuki T, Jenkins NA, Copeland NG, Lenz J. Genome-based identification of cancer genes by proviral tagging in mouse retrovirus-induced T-cell lymphomas. J Virol 2003;77:205-62.
19. Shen H, Suzuki T, Munroe DJ, et al. Common sites of retroviral integration in mouse hematopoietic tumors identified by high-throughput, single nucleotide polymorphism-based mapping and bacterial artificial chromosome/hybridization. J Virol 2003; 77:1584-8.
20. Royer-Pokora B, Rogers M, Zhu T-H, Schneider S, Loos U, Bolitz U. The TTG-2/RBTN2 T cell oncogene encodes two alternative transcripts from two promoters: the distal promoter removed by most 11p13 translocations in acute T cell leukemia's (T-ALL). Oncogene 1995;10:1353-60.
21. Garcia IS, Kaneko Y, Gonzalez-Sarmiento R, et al. A Study of chromosome 11p13 translocations involving TCRβ and TCRδ in human T cell leukaemia. Oncogene 1991; 6:577-82.
22. Rabbitts TH. LMO T-cell translocation oncogenes typify genes activated by chromosomal translocations that alter transcription and developmental processes. Genes Dev 1998;12:2651-7
23. Boehm T, Foroni L, Kennedy M, Rabbitts TH. The rhombotin gene belongs to a class of transcriptional regulators with a potential novel protein dimerisation motif. Oncogene 1990;5:1103-5.
24. Boehm T, Baer R, Lavenir I, et al. The mechanism of chromosomal translocation t(11;14) involving the T-cell receptor Cδ locus on human chromosome 14q11 and a transcribe region of chromosome 11p15. EMBO J 1988;7:385-94.
25. McGuire EA, Hockett RD, Pollock KM, Bartholdi MF, O'Brien SJ, Korsmeyer SJ. The t(11;14)(p15;q11) in a T-cell acute lymphoblastic leukemia cell line activates multiple transcripts, including Ttg-1, a gene encoding a potential zinc finger protein. Mol Cell Biol 1989;9:2124-32.
26. Way JC, Chalfie M. mec-3, A homeobox-containing gene that specifies differentiation of the touch receptor neurons in C. elegans. Cell 1988;54:5-16.
27. Freyd G, Kim SK, Horvitz HR. Novel cysteine-rich motif and homeodomain in the product of the Caenorhabditis elegans cell lineage gene lin-11. Nature 1990;344:876-9.
28. Karlsson O, Thor S, Norberg T, Ohlsson H, Edlund T. Insulin gene enhancer binding protein Isl-1 is a member of a novel class of proteins containing both a homeo- and a Cys-His domain. Nature 1990;334:879-82.
29. Rabbitts TH, Boehm T. LIM domains Nature 1990;346:418.
30. Schmeichel KL, Beekerle MC. The LIM domain is a modular protein-binding interface. Cell 1994;79:211-9.
31. Valge-Archer VE, Osada H, Warren AJ, et al. The LIM protein RBTN2 and the basic helix-loop-helix protein TAL1 are present in a complex in erythroid cells. Proc Natl Acad Sci U S A 1994;91:8617-21.
32. Michelsen JW, Schmeichel KL, Beckerle MC, Winge DR. The LIM motif defines a specific zinc-binding protein domain. Proc Natl Acad Sci U S A 1993;90:4404-8.
33. Perez-Alvarado GC, Miles C, Michelsen JW, et al. Structure of the carbox-terminal LIM domain from the cysteine rich protein CRP. Nat Struct Biol 1994;1:388-98.
34. Osada H, Grutz G, Axelson H, Forster A, Rabbitts TH. Association of erythroid transcription factors: complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1. Proc Natl Acad Sci U S A 1995; 92:9585-9.
35. Wadman I, Li J, Bash RO, et al. Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia. EMBO J 1994;13:4831-9.
36. Wadman IA, Osada H, Grutz CG, et al. The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-binding complex which includes TAL1, E47, GATA-1, and Ldb1/NLI proteins. EMBO J 1997;16:3145-57.
37. Larson RC, Lavenir I, Larson TA, et al. Protein dimerization between Lmo2 (Rbtn2) and Tal1 alters thymocyte development and potentiates T cell tumorigenesis in transgenic mice. EMBO J 1996;15:1021-7.
38. Grutz G, Bucher K, Lavenir I, Larson T, Larson R, Rabbitts TH. The oncogenic T cell LIM-protein Lmo2 forms part of a DNA binding complex specifically in immature T-cells. EMBO J 1998;17:4594-605.
39. Warren AI, Colledge WH, Carlton MBL, Evans MJ, Smith AJH, Rabbitts TH. The oncogenic cysteine-rich LIM domain protein rbtn2 is essential for erythroid development Cell 1994;78:45-57.
40. Fisch P, Boehm T, Lavenir I, et al. T-cell acute lymphoblastic lymphoma induced in transgenic mice by the RBTN1 and RBTN2 LIM-domain genes. Oncogene 1992;7:2389-97.
41. Larson RC, Fisch P, Larson TA, et al. T cell tumours with disparate phenotype in mice transgenic for Rbtn-2. Oncogene 1994; 9:3675-81.
42. Larson RC, Osada H, Larson TA, Lavenir I, Rabbitts TH. The oncogenic LIM protein Rbtn2 causes thymic developmental aberrations that precede malignancy in transgenic mice. Oncogene 1995;11:853-62.
43. Neale GA, Rehg JE, Goorha RM. Disruption of T-cell differentiation precedes T-cell tumor formation in LMO-2 (rhombotin-2) transgenic mice. Leukemia 1997;11:Suppl 3: 289-90.
44. Idem. Ectopic expression or rhombotin-2 causes selective expansion of CD4-CD8-thymocytes in the thymus and T-cell tumours in transgenic mice. Blood 1995;86:3060-71.
45. McCormack MP, Forster A, Drynan LF, Pannell R, Rabbitts TH. The LMO2 T cell oncogene is activated via chromosomal translocations or retroviral insertion during gene therapy but has no mandatory role in normal T cell development. Mol Cell Biol 2003;23: 9003-13.
46. Fotoni L, Boehm T, White L, et al. The rhombotin gene family encode related LIM-domain proteins whose differing expression suggests multiple roles in mouse development. J Mol Biol 1992;226:747-61.
47. Kenny DA, Jurata LW, Saga Y, Gill GN. Identification and characterization of LMO4, an LMO gene with a novel pattern of expression during embryogenesis. Proc Natl Acad Sci U S A 1998;95:11257-62.
48. Herblot S, Steff A-M, Hugo P, Aplan PD, HoangT. SCL and LMO1 alter thymocyte differentiation: inhibition of E2A-HEB, function and pre-Tα chain expression. Nat Immunol 2000;1:138-44.
49. Yamada Y, Warren AI, Dobson C, Forster A, Pannell R, Rabbitts TH. The T cell leukemia LIM protein Lmo2 is necessary for adult mouse hematopoiesis. Proc Natl Acad Sci U S A 1998;95:3890-5.
50. Check E. Cancer fears cast doubts on future of gene therapy. Nature 2003;421:678.
51. Dube ID, Kamel-Reid S, Yuan CC, et al. A novel human homeobox gene lies at the chromosome 10 breakpoint in lymphoid neoplasias with chromosomal translocation t(10;14). Blood 1991;78:2996-3003.
52. Hatano M, Roberts CWM, Minden M, Crist WM, Korsmeyer SJ. Deregulation of a homeobox gene. HOX11, by the t(10;14) in T cell leukemia. Science 1991;253:79-82.
53. Kennedy MA, Gonzalez-Sarmiento R, Kees UR, et al. HOX11, a homeobox-containing T-cell oncogene on human chromosome 10q24. Proc Natl Acad Sci U S A 1991;88: 8900-4.
54. Lu M, Gong ZY, Shen WF, Ho AD. The tcl-3 proto-oncogene altered by chromosomal translocation in T-cell leukemia codes for a homeobox protein. EMBO J 1991;10: 2905-10.
55. Bernard OA, Busson-LeConiat M, Ballerini P, et al. A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia. Leukemia 2001;15:1495-504.
56. Hansen-Hagge TE, Schafer M, Kiyoi H, et al. Disruption of the RanBP17/Hox11L2 region by recombination with the TCRdelta locus in acute lymphoblastic leukemias with t(5;14)(q34;q11). Leukemia 2002;16:2205-12.
57. MacLeod RA, Nagel S, Kaufmann M, Janssen JW, Drexler HG. Activation of HOX11L2 by juxtaposition with 3′-BCL11B in an acute lymphoblastic leukemia cell line (HPB-ALL) with t(5;14)(q35;q32.2). Genes Chromosomes Cancer 2003;37:84-91.
58. Wang J, Jani-Sait SN, Escalon EA, et al. The t(14;21)(q11.2;q22) chromosomal translocation associated with T-cell acute lymphoblastic leukemia activates the BHLHB1 gene. Proc Natl Acad Sci U S A 2000;97:3497-502.
59. Erikson J, Finger L, Sun L, et al. Deregulation of c-myc by translocation of the α-locus of the T-cell receptor in T-cell leukemias. Science 1986;232:884-6.
60. Mellentinj D, Smith SD, Cleary ML. lyl-1, A novel gene altered by chromosomal translocation in T cell leukemia, codes for a protein with a helix-loop-helix DNA binding motif. Cell 1989;58:77-83.
61. Begley CG, Aplan PD, Davey MP, et al. Chromosomal translocation in a human leukemic stem-cell line disrupts the T-cell antigen receptor δ-chain diversity region and results in a previously unreported fusion transcript. Proc Natl Acad Sci U S A 1989;86: 2031-5.
62. Begley CG, Aplan PD, Denning SM, Haynes BF, Waldmann TA, Kirsch IR. The gene SCL is expressed during early hematopoiesis and encodes a differentiation-related DNA-binding motif. Proc Natl Acad Sci U S A 1989;86:10128-32.
63. Brown L, Cheng JT, Chen Q, et al. Site specific recombination of the tal-1 gene is a common occurrence in human T cell leukemia. EMBO J 1990;9:3343-51.
64. Chen Q, Cheng J-T, Tsai L-H, et al. The tal gene undergoes chromosome translocation in T cell leukemia and potentially encodes a helix-loop-helix protein. EMBO J 1990;9:415-24.
65. Aplan PD, Lombardi DP, Kirsch IR. Structural characterization of SIL, a gene frequently disrupted in T-cell acute lymphoblastic leukemia. Mol Cell Biol 1991;11:5462-9.
66. Xia Y, Brown L, Yang CY-C, et al. TAL2, a helix-loop-helix gene activated by the (7;9)(q34;q32) translocation in human T-cell leukemia. Proc Natl Acad Sci U S A 1991;88: 11416-20.
67. Baer R, TAL1, TAL2 and LYL1: a family of basic helix-loop-helix proteins implicated in T cell acute leukemia. Semin Cancer Biol 1993;4:341-7.
68. Tycko B, Smith SD, Sklar J. Chromosomal translocations joining LCK and TCRB loci in human T cell leukemia. J Exp Med 1991;174:867-73.
69. Burnett RC, David JC, Harden AM, Le Beau MM, Rowley JD, Diaz MO. The LCK gene is involved in the t(1;7)(p34;q34) in the T-cell acute lymphoblastic leukemia derived cell line, HSB-2. Genes Chromosomes Cancer 1991;3:461-7.
70. Ellisen LW, BirdJ, 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;66:649-61.
71. Yamada Y, Pannell R, Forster A, Rabbitts TH. The oncogenic LIM-only transcription factor Lmo2 regulates angiogenesis but not vasculogenesis. Proc Natl Acad Sci U S A 2000;97:320-4.
72. Wu X, Li Y, Crise B, Burgess SM. Transcription start regions in the human genome are favored targets for MLV integration. Science 2003;300:1749-51.
73. Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature 2001;409:860-921. [Errata, Nature 2001;411:565, 720.]
74. Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature 2001;409:860-921. [Errata, Nature 2001;411:565, 720.]
75. Kondo M, Takeshita T, Ishii N, et al. Sharing of the interleukin-2 (IL-2) receptor gamma chain between receptors for IL-2 and IL-4. Science 1993;262:1874-7.
76. Noguchi M, Nakamura Y, Russell SM, et al. Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor. Science 1993;262:1877-80.
77. Russell SM, Keegan AD, Harada N, et al. Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor. Science 1993;262:1880-3.
78. Kondo M, Takeshita T, Higuchi M, et al. Functional participation of the IL-2 receptor gamma chain in IL-7 receptor complexes. Science 1994;263:1453-4.
79. Kimura Y, Takeshita T, Kondo M, et al. Sharing of the IL-2 receptor gamma chain with the functional IL-9 receptor complex. Int Immunol 1995;7:115-20.
80. Touw I, Pouwels K, van Agthoven T, et al. Interleukin-7 is a growth factor of precursor B and T acute lymphoblastic leukemia. Blood 1990;75:2097-101.
81. Barata JT, Cardoso AA, Nadler LM, Boussiotis VA. Interleukin-7 promotes survival and cell cycle progression of T-cell acute lymphoblastic leukemia cells by down-regulating the cyclin-dependent kinase inhibitor p27(kip1). Blood 2001;98:1524-31.
82. Karawajew L, Ruppert V, Wuchter C, et al. Inhibition of in vitro spontaneous apoptosis by IL-7 correlates with bcl-2 up-regulation, cortical/mature immunophenotype, and better early cytoreduction of childhood T-cell acute lymphoblastic leukemia. Blood 2000; 96:297-306.
83. Lando Z, Sarin P, Megson M, et al. Association of human T-cell leukaemia/lymphoma virus with the Tac antigen marker for the human T-cell growth factor receptor. Nature 1983;305:733-6.
84. Maruyama M, Shibuya H, Harada H, et al. Evidence for aberrant activation of the interleukin-2 autocrine loop by HTLV-1-encoded p40x and T3/Ti complex triggering. Cell 1987;48:343-50.
85. Greaves MF. Speculations on the cause of childhood acute lymphoblastic leukemia. Leukemia 1998;2:120-5.
86. Idem. Models of childhood acute lymphoblastic leakemia: Leukemia 1991;5:819-20.
87. Greaves MF, Alexander FE. An infectious etiology for common acute lymphoblastic leukemia in childhood? Leukemia 1993;7: 349-60.
88. Drynan LF, Hamilton TL, Rabbitts TH. T cell tumorigenesis in Lmo2 transgenic mice is independent of V-D-J recombinase activity. Oncogene 2001;20:4412-5.
89. Boehm T, Buluwela L, Williams D, White L, Rabbitts TH. A cluster of chromosome 11p13 translocations found via distinc D-D and D-D-J rearrangements of the human T cell receptor δ chain gene. EMBO J 1998; 7:2011-7.
90. Baum C, Dullman J, Li Z, et al. Side effects of retroviral gene transfer into hematopoietic stem cells. Blood 2003;101:2099-114.