Load and lock: The molecular mechanisms of B-lymphocyte commitment

Immunological Reviews

Volumn 238, Issue 1, 2010, Pages 47-62

  Zandi, Sasan ^a   Bryder, David ^b   Sigvardsson, Mikael ^a  

^a LINKÖPING UNIVERSITY   (Sweden)

^b LUND UNIVERSITY   (Sweden)

Author keywords

B cells; Cancer; Cell differentiation; Hematopoiesis; Hematopoietic progenitor cells; Transcription factors

Indexed keywords

ARTICLE; B LYMPHOCYTE; B LYMPHOCYTE DIFFERENTIATION; CELL DIFFERENTIATION; CELL FATE; CELL LINEAGE; CELL MATURATION; CELL SELECTION; DNA BINDING; EPIGENETICS; GENE EXPRESSION; HEMATOPOIESIS; HEMATOPOIETIC STEM CELL; HUMAN; IMMUNE DEFICIENCY; LEUKEMIA; LYMPHOID CELL; LYMPHOMA; LYMPHOPOIESIS; MALIGNANT TRANSFORMATION; MULTIPOTENT STEM CELL; NONHUMAN; PRIORITY JOURNAL; REGULATORY MECHANISM;

ANIMALS; ANTIGENS, DIFFERENTIATION; B-LYMPHOCYTES; CELL LINEAGE; CELL TRANSFORMATION, NEOPLASTIC; GENE EXPRESSION REGULATION; HEMATOPOIESIS; HUMANS; SIGNAL TRANSDUCTION;

EID: 77958542905     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/j.1600-065X.2010.00950.x     Document Type: Article

References (162)

1. Jhunjhunwala S, et al. The 3D structure of the immunoglobulin heavy-chain locus: implications for long-range genomic interactions. Cell 2008;133:265-279.
2. Jhunjhunwala S, Van Zelm MC, Peak MM, Murre C. Chromatin architecture and the generation of antigen receptor diversity. Cell 2009;138:435-448.
3. Schebesta A, McManus S, Salvagiotto G, Delogu A, Busslinger GA, Busslinger M. Transcription factor Pax5 activates the chromatin of key genes involved in B cell signaling, adhesion, migration, and immune function. Immunity 2007;27:49-63.
4. Treiber T, et al. Early B cell factor 1 regulates B cell gene networks by activation, repression, and transcription- independent poising of chromatin. Immunity 2010;32:714-725.
5. Lin YC, et al. A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate. Nat Immunol 2010;11:635-643.
6. Murre C. Developmental trajectories in early hematopoiesis. Genes Dev 2009;23:2366-2370.
7. Ikuta K, Weissman IL. Evidence that hematopoietic stem cells express mouse c-kit but do not depend on steel factor for their generation. Proc Natl Acad Sci USA 1992;89:1502-1506.
8. Li CL, Johnson GR. Murine hematopoietic stem and progenitor cells: I. Enrichment and biologic characterization. Blood 1995;85:1472-1479.
9. Osawa M, Hanada K, Hamada H, Nakauchi H. Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science 1996;273:242-245.
10. Christensen JL, Weissman IL. Flk-2 is a marker in hematopoietic stem cell differentiation: a simple method to isolate long-term stem cells. Proc Natl Acad Sci USA 2001;98:14541-14546.
11. Adolfsson J, et al. Upregulation of Flt3 expression within the bone marrow Lin(-)Sca1(+)c-kit(+) stem cell compartment is accompanied by loss of self-renewal capacity. Immunity 2001;15:659-669.
12. Yang L, et al. Identification of Lin(-)Sca1(+)kit(+)CD34(+)Flt3- short-term hematopoietic stem cells capable of rapidly reconstituting and rescuing myeloablated transplant recipients. Blood 2005;105:2717-2723.
13. Adolfsson J, et al. Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment. Cell 2005;121:295-306.
14. Rossi DJ, et al. Cell intrinsic alterations underlie hematopoietic stem cell aging. Proc Natl Acad Sci USA 2005;102:9194-9199.
15. Lescale C, et al. Reduced EBF expression underlies loss of B cell potential of hematopoietic progenitors with age. Aging Cell 2010;9:410-419.
16. Akashi K, Traver D, Miyamoto T, Weissman IL. A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 2000;404:193-197.
17. Pronk C, et al. Elucidation of the phenotype, functional, and molecular topography of a myeloerythroid progenitor cell hierarchy. Cell Stem Cell 2007;1:428-442.
18. Kondo M, Weissman IL, Akashi K. Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 1997;91:661-672.
19. Allman D, et al. Thymopoiesis independent of common lymphoid progenitors. Nat Immunol 2003;4:168-174.
20. Katsura Y, Kawamoto H. Stepwise lineage restriction of progenitors in lympho-myelopoiesis. Int Rev Immunol 2001;20:1-20.
21. Wada H, et al. Adult T-cell progenitors retain myeloid potential. Nature 2008;452:768-772.
22. Bell JJ, Bhandoola A. The earliest thymic progenitors for T cells possess myeloid lineage potential. Nature 2008;452:764-767.
23. Montecino-Rodriguez E, Leathers H, Dorshkind K. Bipotential B-macrophage progenitors are present in adult bone marrow. Nat Immunol 2001;2:83-88.
24. Hartenstein V. Blood cells and blood cell development in the animal kingdom. Annu Rev Cell Dev Biol 2006;22:677-712.
25. Xie H, Ye M, Feng R, Graf T. Stepwise reprogramming of B cells into macrophages. Cell 2004;117:663-676.
26. Nutt SL, Heavey B, Rolink AG, Busslinger M. Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature 1999;401:556-562.
27. Cobaleda C, Jochum W, Busslinger M. Conversion of mature B cells into T cells by dedifferentiation to uncommitted progenitors. Nature 2007;449:473-477.
28. Laiosa CV, Stadtfeld M, Xie H, De Andres-Aguayo L, Graf T. Reprogramming of committed T cell progenitors to macrophages and dendritic cells by C/EBP alpha and PU.1 transcription factors. Immunity 2006;25:731-744.
29. Pongubala JM, et al. Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5. Nat Immunol 2008;9:203-215.
30. Graf T, Enver T. Forcing cells to change lineages. Nature 2009;462:587-594.
31. Cui K, et al. Chromatin signatures in multipotent human hematopoietic stem cells indicate the fate of bivalent genes during differentiation. Cell Stem Cell 2009;4:80-93.
32. Attema JL, Papathanasiou P, Forsberg EC, Xu J, Smale ST, Weissman IL. Epigenetic characterization of hematopoietic stem cell differentiation using miniChIP and bisulfite sequencing analysis. Proc Natl Acad Sci USA 2007;104:12371-12376.
33. Weishaupt H, Sigvardsson M, Attema JL. Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells. Blood 2010;114:247-256.
34. Park IK, et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 2003;423:302-305.
35. Iwama A, et al. Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1. Immunity 2004;21:843-851.
36. Kamminga LM, et al. The Polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion. Blood 2006;107:2170-2179.
37. Vire E, et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature 2006;439:871-874.
38. Broske AM, et al. DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction. Nat Genet 2009;41:1207-1215.
39. Oguro H, et al. Poised lineage specification in multipotential hematopoietic stem and progenitor cells by the polycomb protein Bmi1. Cell Stem Cell 2010;6:279-286.
40. DeKoter RP, Singh H. Regulation of B lymphocyte and macrophage development by graded expression of PU.1. Science 2000;288:1439-1441.
41. Spooner CJ, Cheng JX, Pujadas E, Laslo P, Singh H. A recurrent network involving the transcription factors PU.1 and Gfi1 orchestrates innate and adaptive immune cell fates. Immunity 2009;31:576-586.
42. Laslo P, et al. Multilineage transcriptional priming and determination of alternate hematopoietic cell fates. Cell 2006;126:755-766.
43. Wang JH, et al. Selective defects in the development of the fetal and adult lymphoid system in mice with an Ikaros null mutation. Immunity 1996;5:537-549.
44. Yoshida T, Ng SY, Zuniga-Pflucker JC, Georgopoulos K. Early hematopoietic lineage restrictions directed by Ikaros. Nat Immunol 2006;7:382-391.
45. Igarashi H, Gregory SC, Yokota T, Sakaguchi N, Kincade PW. Transcription from the RAG1 locus marks the earliest lymphocyte progenitors in bone marrow. Immunity 2002;17:117-130.
46. Tudor KS, Payne KJ, Yamashita Y, Kincade PW. Functional assessment of precursors from murine bone marrow suggests a sequence of early B lineage differentiation events. Immunity 2000;12:335-345.
47. Mansson R, et al. Molecular evidence for hierarchical transcriptional lineage priming in fetal and adult stem cells and multipotent progenitors. Immunity 2007;26:407-419.
48. Ng SY, Yoshida T, Zhang J, Georgopoulos K. Genome-wide lineage-specific transcriptional networks underscore Ikaros-dependent lymphoid priming in hematopoietic stem cells. Immunity 2009;30:493-507.
49. Hu M, et al. Multilineage gene expression precedes commitment in the hemopoietic system. Genes Dev 1997;11:774-785.
50. Bernstein BE, et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 2006;125:315-326.
51. Choi JK, Shen C-P, Radomska HS, Eckhardt LA, Kadesch T. E47 activates the Ig-heavy chain and TdT loci in non-B cells. EMBO J 1996;15:5014-5021.
52. Schlissel M, Voronova A, Baltimore D. Helix-loop-helix transcription factor E47 activates germ-line immunoglobulin heavy-chain gene transcription and rearrangement in a pre-T-cell line. Genes Dev 1991;5:1367-1376.
53. Zhuang Y, Soriano P, Weintraub H. The helix-loop-helix gene E2A is required for B cell formation. Cell 1994;79:875-884.
54. Bain G, et al. E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements. Cell 1994;79:885-892.
55. Semerad CL, Mercer EM, Inlay MA, Weissman IL, Murre C. E2A proteins maintain the hematopoietic stem cell pool and promote the maturation of myelolymphoid and myeloerythroid progenitors. Proc Natl Acad Sci USA 2009;106:1930-1935.
56. Dias S, Mansson R, Gurbuxani S, Sigvardsson M, Kee BL. E2A proteins promote development of lymphoid-primed multipotent progenitors. Immunity 2008;29:217-227.
57. Mansson R, et al. B-lineage commitment prior to surface expression of B220 and CD19 on hematopoietic progenitor cells. Blood 2008;112:1048-1055.
58. Mansson R, et al. Single-cell analysis of the common lymphoid progenitor compartment reveals functional and molecular heterogeneity. Blood 2010;115:2601-2609.
59. Li YS, Wasserman R, Hayakawa K, Hardy RR. Identification of the earliest B lineage stage in mouse bone marrow. Immunity 1996;5:527-535.
60. Hardy RR, Hayakawa K. B-lineage differentiation stages resolved by multiparameter flow cytometry. Ann NY Acad Sci 1995;764:19-24.
61. Hardy RR, Carmack CE, Shinton SA, Kemp JD, Hayakawa K. Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow. J Exp Med 1991;173:1213-1225.
62. Rumfelt LL, Zhou Y, Rowley BM, Shinton SA, Hardy RR. Lineage specification and plasticity in CD19- early B cell precursors. J Exp Med 2006;203:675-687.
63. Fuxa M, Busslinger M. Reporter gene insertions reveal a strictly B lymphoid-specific expression pattern of Pax5 in support of its B cell identity function. J Immunol 2007;178:3031-3037.
64. Martensson IL, Melchers F, Winkler TH. A transgenic marker for mouse B lymphoid precursors. J Exp Med 1997;185:653-661.
65. Inlay MA, et al. Ly6d marks the earliest stage of B-cell specification and identifies the branchpoint between B-cell and T-cell development. Genes Dev 2009;23:2376-2381.
66. Martin CH, et al. Efficient thymic immigration of B220+ lymphoid-restricted bone marrow cells with T precursor potential. Nat Immunol 2003;4:866-873.
67. Nutt SL, Kee BL. The transcriptional regulation of B cell lineage commitment. Immunity 2007;26:715-725.
68. Hagman J, Belanger C, Travis A, Turck CW, Grosschedl R. Cloning and functional characterization of early B-cell factor, a regulator of lymphocyte-specific gene expression. Genes Dev 1993;7:760-773.
69. Wang MM, Reed RR. Molecular cloning of the olfactory neuronal transcription factor Olf-1 by genetic selection in yeast. Nature 1993;364:121-126.
70. Wang SS, Tsai RYL, Reed RR. The characterization of the Olf-1/EBF-like HLH transcription factor family: implications in olfactory gene regulation and neuronal development. J Neurosci 1997;17:4149-4158.
71. Akerblad P, Lind U, Liberg D, Bamberg K, Sigvardsson M. Early B-cell factor (o/e-1) is a promoter of adipogenesis and involved in control of genes important for terminal adipocyte differentiation. Mol Cell Biol 2002;22:8015-8025.
72. Lagergren A, et al. The Cxcl12, periostin, and Ccl9 genes are direct targets for early B-cell factor in OP-9 stroma cells. J Biol Chem 2007;282:14454-14462.
73. Kieslinger M, et al. EBF2 regulates osteoblast-dependent differentiation of osteoclasts. Dev Cell 2005;9:757-767.
74. Lin H, Grosschedl R. Failure of B-cell differentiation in mice lacking the transcription factor EBF. Nature 1995;376:263-267.
75. Dias S, Silva H Jr, Cumano A, Vieira P. Interleukin-7 is necessary to maintain the B cell potential in common lymphoid progenitors. J Exp Med 2005;201:971-979.
76. Zandi S, Mansson R, Tsapogas P, Zetterblad J, Bryder D, Sigvardsson M. EBF1 is essential for B-lineage priming and establishment of a transcription factor network in common lymphoid progenitors. J Immunol 2008;181:3364-3372.
77. Schubart DB, Rolink A, Kosco-Vilbois M, Botteri F, Matthias P. B-cell-specific coactivator OBF/OCA-B/Bob-1 required for immune response and germinal center formation. Nature 1996;383:538-542.
78. Kim U, et al. The B-cell-specific transcription coactivator OCA-B/OBF-1/Bob-1 is essential for normal production of immunoglobulin isotypes. Nature 1996;383:542-547.
79. Hess J, Nielsen PJ, Fischer KD, Bujard H, Wirth T. The B lymphocyte-specific coactivator BOB.1/OBF.1 is required at multiple stages of B-cell development. Mol Cell Biol 2001;21:1531-1539.
80. Dengler HS, et al. Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation. Nat Immunol 2008;9:1388-1398.
81. Amin RH, Schlissel MS. Foxo1 directly regulates the transcription of recombination-activating genes during B cell development. Nat Immunol 2008;9:613-622.
82. Sigvardsson M, O'Riordan M, Grosschedl R. EBF and E47 collaborate to induce expression of the endogenous immunoglobulin surrogate light chain genes. Immunity 1997;7:25-36.
83. Travis A, Hagman J, Grosschedl R. Heterogeneously initiated transcription from the pre-B- and B-cell- specific mb-1 promoter: analysis of the requirement for upstream factor- binding sites and initiation site sequences. Mol Cell Biol 1991;11:5756-5766.
84. Feldhaus AL, Mbangkollo D, Arvin KL, Klug CA, Singh H. BLyF, a novel cell-type- and stage-specific regulator of the B- lymphocyte gene mb-1. Mol Cell Biol 1992;12:1126-1133.
85. Sigvardsson M, et al. Early B-cell factor, E2A, and Pax-5 cooperate to activate the early B cell-specific mb-1 promoter. Mol Cell Biol 2002;22:8539-8551.
86. Maier H, et al. Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription. Nat Immunol 2004;5:1069-1077.
87. Walter K, Bonifer C, Tagoh H. Stem cell-specific epigenetic priming and B cell-specific transcriptional activation at the mouse Cd19 locus. Blood 2008;112:1673-1682.
88. Adams B, et al. Pax-5 encodes the transcription factor BSAP and is expressed in B lymphocytes, the developing CNS, and adult testis. Genes Dev 1992;6:1589-1607.
89. Smith EM, Gisler R, Sigvardsson M. Cloning and characterization of a promoter flanking the early B cell factor (EBF) gene indicates roles for E-proteins and autoregulation in the control of EBF expression. J Immunol 2002;169:261-270.
90. Roessler S, et al. Distinct promoters mediate the regulation of Ebf1 gene expression by interleukin-7 and Pax5. Mol Cell Biol 2007;27:579-594.
91. Von Freeden-Jeffry U, Vieira P, Lucian LA, McNeil T, Burdach SE, Murray R. Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J Exp Med 1995;181:1519-1526.
92. Kikuchi K, Lai AY, Hsu CL, Kondo M. IL-7 receptor signaling is necessary for stage transition in adult B cell development through up-regulation of EBF. J Exp Med 2005;201:1197-1203.
93. Malin S, et al. Role of STAT5 in controlling cell survival and immunoglobulin gene recombination during pro-B cell development. Nat Immunol 2010;11:171-179.
94. Akashi K, Kondo M, Von Freeden-Jeffry U, Murray R, Weissman IL. Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice. Cell 1997;89:1033-1041.
95. Goetz CA, Harmon IR, O'Neil JJ, Burchill MA, Johanns TM, Farrar MA. Restricted STAT5 activation dictates appropriate thymic B versus T cell lineage commitment. J Immunol 2005;174:7753-7763.
96. Welner RS, et al. Asynchronous RAG-1 expression during B lymphopoiesis. J Immunol 2009;183:7768-7777.
97. Decker T, et al. Stepwise activation of enhancer and promoter regions of the B cell commitment gene Pax5 in early lymphopoiesis. Immunity 2009;30:508-520.
98. O'Riordan M, Grosschedl R. Coordinate regulation of B cell differentiation by the transcription factors EBF and E2A. Immunity 1999;11:21-31.
99. Smith EM, Akerblad P, Kadesch T, Axelson H, Sigvardsson M. Inhibition of EBF function by active Notch signaling reveals a novel regulatory pathway in early B-cell development. Blood 2005;106:1995-2001.
100. Radtke F, et al. Deficient T cell fate specification in mice with an induced inactivation of Notch1. Immunity 1999;10:547-558.
101. Pui JC, et al. Notch1 expression in early lymphopoiesis influences B versus T lineage determination. Immunity 1999;11:299-308.
102. Maeda T, et al. Regulation of B versus T lymphoid lineage fate decision by the proto-oncogene LRF. Science 2007;316:860-866.
103. Nie L, Xu M, Vladimirova A, Sun XH. Notch-induced E2A ubiquitination and degradation are controlled by MAP kinase activities. EMBO J 2003;22:5780-5792.
104. Thal MA, et al. Ebf1-mediated down-regulation of Id2 and Id3 is essential for specification of the B cell lineage. Proc Natl Acad Sci USA 2009;106:552-557.
105. Souabni A, Cobaleda C, Schebesta M, Busslinger M. Pax5 promotes B lymphopoiesis and blocks T cell development by repressing Notch1. Immunity 2002;17:781-793.
106. Urbánek P, Wang Z-Q, Fetka I, Wagner EF, Busslinger M. Complete block of early B cell differentiation and altered patterning of the posterior midbrain in mice lacking Pax5/BSAP. Cell 1994;79:901-912.
107. Nutt SL, Urbanek P, Rolink A, Busslinger M. Essential functions of Pax5 (BSAP) in pro-B cell development: difference between fetal and adult B lymphopoiesis and reduced V-to-DJ recombination at the IgH locus. Genes Dev 1997;11:476-491.
108. Rolink AG, Nutt SL, Melchers F, Busslinger M. Long-term in vivo reconstitution of T-cell development by Pax5- deficient B-cell progenitors. Nature 1999;401:603-606.
109. Tagoh H, et al. The mechanism of repression of the myeloid-specific c-fms gene by Pax5 during B lineage restriction. EMBO J 2006;25:1070-1080.
110. Reynaud D, et al. Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros. Nat Immunol 2008;9:927-936.
111. Ikawa T, Kawamoto H, Wright LY, Murre C. Long-term cultured E2A-deficient hematopoietic progenitor cells are pluripotent. Immunity 2004;20:349-360.
112. Kwon K, et al. Instructive role of the transcription factor E2A in early B lymphopoiesis and germinal center B cell development. Immunity 2008;28:751-762.
113. Seet CS, Brumbaugh RL, Kee BL. Early B cell factor promotes B lymphopoiesis with reduced interleukin 7 responsiveness in the absence of E2A. J Exp Med 2004;199:1689-1700.
114. Montecino-Rodriguez E, Leathers H, Dorshkind K. Identification of a B-1 B cell-specified progenitor. Nat Immunol 2006;7:293-301.
115. Haas KM, Poe JC, Steeber DA, Tedder TF. B-1a and B-1b cells exhibit distinct developmental requirements and have unique functional roles in innate and adaptive immunity to S. pneumoniae. Immunity 2005;23:7-18.
116. Hardy RR, Hayakawa K. A developmental switch in B lymphopoiesis. Proc Natl Acad Sci USA 1991;88:11550-11554.
117. Esplin BL, Welner RS, Zhang Q, Borghesi LA, Kincade PW. A differentiation pathway for B1 cells in adult bone marrow. Proc Natl Acad Sci USA 2009;106:5773-5778.
118. Wong PM, Chung SW, Chui DH, Eaves CJ. Properties of the earliest clonogenic hemopoietic precursors to appear in the developing murine yolk sac. Proc Natl Acad Sci USA 1986;83:3851-3854.
119. Ikuta K, et al. A developmental switch in thymic lymphocyte maturation potential occurs at the level of hematopoietic stem cells. Cell 1990;62:863-874.
120. Weksler ME, Szabo P. The effect of age on the B-cell repertoire. J Clin Immunol 2000;20:240-249.
121. Linton PJ, Dorshkind K. Age-related changes in lymphocyte development and function. Nat Immunol 2004;5:133-139.
122. Stephan RP, Sanders VM, Witte PL. Stage-specific alterations in murine B lymphopoiesis with age. Int Immunol 1996;8:509-518.
123. Stephan RP, Reilly CR, Witte PL. Impaired ability of bone marrow stromal cells to support B-lymphopoiesis with age. Blood 1998;91:75-88.
124. Labrie JE 3rd, Sah AP, Allman DM, Cancro MP, Gerstein RM. Bone marrow microenvironmental changes underlie reduced RAG-mediated recombination and B cell generation in aged mice. J Exp Med 2004;200:411-423.
125. Guerrettaz LM, Johnson SA, Cambier JC. Acquired hematopoietic stem cell defects determine B-cell repertoire changes associated with aging. Proc Natl Acad Sci USA 2008;105:11898-11902.
126. Sudo K, Ema H, Morita Y, Nakauchi H. Age-associated characteristics of murine hematopoietic stem cells. J Exp Med 2000;192:1273-1280.
127. Sitnicka E, Bryder D, Theilgaard-Monch K, Buza-Vidas N, Adolfsson J, Jacobsen SE. Key role of flt3 ligand in regulation of the common lymphoid progenitor but not in maintenance of the hematopoietic stem cell pool. Immunity 2002;17:463-472.
128. Attema JL, Pronk CJ, Norddahl GL, Nygren JM, Bryder D. Hematopoietic stem cell ageing is uncoupled from p16 INK4A-mediated senescence. Oncogene 2009;28:2238-2243.
129. Staudt LM. Molecular diagnosis of the hematologic cancers. N Engl J Med 2003;348:1777-1785.
130. Shaffer AL, Rosenwald A, Staudt LM. Lymphoid malignancies: the dark side of B-cell differentiation. Nat Rev Immunol 2002;2:920-932.
131. Kuppers R, Dalla-Favera R. Mechanisms of chromosomal translocations in B cell lymphomas. Oncogene 2001;20:5580-5594.
132. Kuppers R. Mechanisms of B-cell lymphoma pathogenesis. Nat Rev Cancer 2005;5:251-262.
133. Tsujimoto Y, Cossman J, Jaffe E, Croce CM. Involvement of the bcl-2 gene in human follicular lymphoma. Science 1985;228:1440-1443.
134. Tsujimoto Y, Gorham J, Cossman J, Jaffe E, Croce CM. The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining. Science 1985;229:1390-1393.
135. Rabbitts TH, Hamlyn PH, Baer R. Altered nucleotide sequences of a translocated c-myc gene in Burkitt lymphoma. Nature 1983;306:760-765.
136. Kamps MP, Look AT, Baltimore D. The human t(1;19) translocation in pre-B ALL produces multiple nuclear E2A-Pbx1 fusion proteins with differing transforming potentials. Genes Dev 1991;5:358-368.
137. Dedera DA, et al. Chimeric homeobox gene E2A-PBX1 induces proliferation, apoptosis, and malignant lymphomas in transgenic mice. Cell 1993;74:833-843.
138. Ferrando AA, Look AT. Clinical implications of recurring chromosomal and associated molecular abnormalities in acute lymphoblastic leukemia. Semin Hematol 2000;37:381-395.
139. Andreasson P, Schwaller J, Anastasiadou E, Aster J, Gilliland DG. The expression of ETV6/CBFA2 (TEL/AML1) is not sufficient for the transformation of hematopoietic cell lines in vitro or the induction of hematologic disease in vivo. Cancer Genet Cytogenet 2001;130:93-104.
140. O'Neil J, Look AT. Mechanisms of transcription factor deregulation in lymphoid cell transformation. Oncogene 2007;26:6838-6849.
141. Mullighan CG, et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 2007;446:758-764.
142. Iida S, et al. The t(9;14)(p13;q32) chromosomal translocation associated with lymphoplasmacytoid lymphoma involves the PAX-5 gene. Blood 1996;88:4110-4117.
143. Busslinger M, Klix N, Pfeffer P, Graninger PG, Kozmik Z. Deregulation of PAX-5 by translocation of the Emu enhancer of the IgH locus adjacent to two alternative PAX-5 promoters in a diffuse large-cell lymphoma. Proc Natl Acad Sci USA 1996;93:6129-6134.
144. Yang JJ, et al. Genome-wide copy number profiling reveals molecular evolution from diagnosis to relapse in childhood acute lymphoblastic leukemia. Blood 2008;112:4178-4183.
145. Raval A, et al. Downregulation of death-associated protein kinase 1 (DAPK1) in chronic lymphocytic leukemia. Cell 2007;129:879-890.
146. Katzenellenbogen RA, Baylin SB, Herman JG. Hypermethylation of the DAP-kinase CpG island is a common alteration in B-cell malignancies. Blood 1999;93:4347-4353.
147. Baur AS, Shaw P, Burri N, Delacretaz F, Bosman FT, Chaubert P. Frequent methylation silencing of p15(INK4b) (MTS2) and p16(INK4a) (MTS1) in B-cell and T-cell lymphomas. Blood 1999;94:1773-1781.
148. Kuang SQ, et al. Genome-wide identification of aberrantly methylated promoter associated CpG islands in acute lymphocytic leukemia. Leukemia 2008;22:1529-1538.
149. Shen L, et al. Aberrant DNA methylation of p57KIP2 identifies a cell-cycle regulatory pathway with prognostic impact in adult acute lymphocytic leukemia. Blood 2003;101:4131-4136.
150. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004;116:281-297.
151. Chen CZ, Li L, Lodish HF, Bartel DP. MicroRNAs modulate hematopoietic lineage differentiation. Science 2004;303:83-86.
152. Koralov SB, et al. Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage. Cell 2008;132:860-874.
153. Ventura A, et al. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell 2008;132:875-886.
154. Xiao C, et al. MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb. Cell 2007;131:146-159.
155. Zhou B, Wang S, Mayr C, Bartel DP, Lodish HF. miR-150, a microRNA expressed in mature B and T cells, blocks early B cell development when expressed prematurely. Proc Natl Acad Sci USA 2007;104:7080-7085.
156. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer 2006;6:857-866.
157. Calin GA, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2002;99:15524-15529.
158. Mi S, et al. MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proc Natl Acad Sci USA 2007;104:19971-19976.
159. Roman-Gomez J, et al. Epigenetic regulation of microRNAs in acute lymphoblastic leukemia. J Clin Oncol 2009;27:1316-1322.
160. Liu P, et al. Bcl11a is essential for normal lymphoid development. Nat Immunol 2003;4:525-532.
161. Greig KT, et al. Critical roles for c-Myb in lymphoid priming and early B-cell development. Blood 2010;115:2796-2805.
162. Hu H, et al. Foxp1 is an essential transcriptional regulator of B cell development. Nat Immunol 2006;7:819-826.