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Retinoic acid receptors in normal and neoplastic haematopoietic cells

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Vitamin A and Retinoids: An Update of Biological Aspects and Clinical Applications

Part of the book series: MCBU Molecular and Cell Biology Updates ((MCBU))

Abstract

Haemopoiesis is the process by which the multiple cell lineages that constitute blood arise from a small pool of multipotent haematopoietic stem cells. Although the formation of stable transcription complexes that initiate and consolidate exclusive programmes of gene expression must play a key role in this process, exactly how a multipotential cell chooses a particular lineage remains poorly understood. Transcription factors, such as retinoid receptors and Kriippel related Zinc (Zn)-finger proteins, play important roles in a wide range of cellular processes [1-7]. Characterisation of a large number of mutations/chromosomal translocations which are associated with haematopoietic neoplasms have, in the majority of cases, identified transcription factors, including members of the above mentioned gene families, which play important roles in haemopoiesis and which serve as direct targets of oncogenic processes [8,9]. Nevertheless, despite the molecular cloning of a plethora of translocation-generated fusion genes, which encode chimeric transcription factors, the mechanisms of leukaemogenesis remain obscure. Recent work from our and other laboratories on acute promyelocytic leukaemia (APL) has provided a major insight into the molecular pathogenesis of a haematopoietic neoplasm and the basis for its response to a number of currently-used or potential therapeutic agents (see below).

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References

  1. Schneider-Maunoury S, Topilko P, Seitanidou T, Levi G, Cohen-Tannoudji M, Pournin S, Babinet C, Charnay P (1993) Disruption of Krox-20 results in alteration of rhombomeres 3 and 5 in the developing hindbrain. Cell 75: 1199–1214

    Article  PubMed  CAS  Google Scholar 

  2. El-Baradi T, Pieler T (1991) Zinc finger proteins: what we know and what we would like to know. Mech Develop 35: 155–169

    Article  CAS  Google Scholar 

  3. Lee SL, Wang Y, Milbrandt J (1996) Unimpaired macrophage differentiation and activation in mice lacking the zinc finger transplantation factor NGFI-A (EGR1). Mol Cell Biol 16: 4566–4572

    PubMed  CAS  Google Scholar 

  4. Perrotti D, Melotti P, Skorski T, Casella I, Peschle C, Calabretta B (1995) Overexpression of the zinc finger protein MZF1 inhibits hematopoietic development from embryonic stem cells: correlation with negative regulation of CD34 and c-myb promoter activity. Mol Cell Biol 15: 6075–6087

    PubMed  CAS  Google Scholar 

  5. Shivdasani RA, Orkin SH (1996) The transcriptional control of hematopoiesis. Blood 87: 4025–4039

    PubMed  CAS  Google Scholar 

  6. Wade PA, Pruss D, Wolfe AP (1997) Histone acetylation: chromatin in action. Trends Biochem Sci 22: 128–132

    Article  PubMed  CAS  Google Scholar 

  7. Kastner P, Mark M, Chambon P (1995) Nonsteroid nuclear receptors—What Are genetic studies telling us about their role in real life. Cell 83: 859–869

    Article  PubMed  CAS  Google Scholar 

  8. Look A (1997) Oncogenic transcription factors in the human acute leukemias. Science 278: 1059–1064

    Article  PubMed  CAS  Google Scholar 

  9. Rabbins TH (1994) Chromsomal translocations in human cancer. Nature 372: 143–149

    Article  Google Scholar 

  10. Orphanides G, Lagrange T, Reinberg D (1996) The general transcription factors of RNA polymerase II. Gene Develop 10: 2657–2683

    Article  CAS  Google Scholar 

  11. Roeder RG (1996) The role of general initiation factors in transcription by RNA polymerase II. Trends Biochem Sci 21: 327–335

    PubMed  CAS  Google Scholar 

  12. Verrijzer CP, Tjian R (1996) TAFs mediate transcriptional activation and promoter selectivity. Trends Biochem Sci 21: 338–342

    Article  PubMed  CAS  Google Scholar 

  13. Ptashne M, Gann A (1997) Transcriptional activation by recruitment. Nature 386: 569–577

    Article  PubMed  CAS  Google Scholar 

  14. Dove SL, Joung JK, Hochschild A (1997) Activation of prokaryotic transcription through arbitrary protein-protein contacts. Nature 386: 627–630

    Article  PubMed  CAS  Google Scholar 

  15. Janknecht R, Hunter T (1996) Versatile molecular glue. Transcriptional control. Curr Biol 6: 951–954

    Article  PubMed  CAS  Google Scholar 

  16. Janknecht R, Hunter T (1996) A growing coactivator network. Nature 383: 22–23

    Article  PubMed  CAS  Google Scholar 

  17. Vettesedadey M, Grant PA, Hebbes TR, Cranerobinson C, Allis CD, Workman JL (1996) Acetylation of histone H4 plays a primary role in enhancing transcription factor-binding to nucleosomal DNA in vitro. EMBO J 15: 2508–2518

    CAS  Google Scholar 

  18. Grunstein M (1997) Histone acetylation in chromatin structure and transcription. Nature 389: 349–352

    Article  PubMed  CAS  Google Scholar 

  19. Montminy M (1997) Something new to hang your HAT on. Nature 387: 654–655

    Article  PubMed  CAS  Google Scholar 

  20. Torchia J, Rose DW, Inostroza J, Kamei Y, Westin S, Glass CK, Rosenfeld MG (1997) The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function. Nature 387: 677–684

    Article  PubMed  CAS  Google Scholar 

  21. Pazin MJ, Kadonaga JT (1997) SWI2/SNF2 and related proteins: ATP-driven motors that disrupt protein-DNA interactions? Cell 88: 737–740

    Article  PubMed  CAS  Google Scholar 

  22. Peterson CL (1996) Multiple SWItches to turn on chromatin? Curr Opin Genet Develop 6: 171–175

    Article  CAS  Google Scholar 

  23. Yoshinaga SK, Peterson CL, Herskowitz I, Yamamoto KR (1992) Roles of SWI1, SWI2, and SWI3 proteins for transcriptional enhancement by steroid receptors. Science 258: 1598–1604

    Article  PubMed  CAS  Google Scholar 

  24. Wilson CJ, Chao DM, Imbalzano AN, Schnitzler GR, Kingston RE, Young RA (1996) RNA polymerase II holoenzyme contains SWI/SNF regulators involved in chromatin remodeling. Cell 84: 235–244

    Article  PubMed  CAS  Google Scholar 

  25. Wolffe AP (1997) Sinful repression. Nature 387: 16–17

    Article  PubMed  CAS  Google Scholar 

  26. DePinho R (1998) Transcriptional repression. The cancer-chromatin connection. Nature 391: 535–536

    Article  Google Scholar 

  27. Bestor TH (1998) Gene silencing. Methylation meets acetylation. Nature 393: 311–312

    Article  PubMed  CAS  Google Scholar 

  28. Wolbach SB, Howe PR (1925) Tissue changes following deprivation of fat-soluble A vitamin. J Exp Med 42: 753–777

    Article  PubMed  CAS  Google Scholar 

  29. Chambon P (1996) A decade of molecular biology of retinoic acid receptors. FASEB J 10: 940–954

    PubMed  CAS  Google Scholar 

  30. Wen DX, McDonnell DP (1995) Advances in our understanding of ligand-activated nuclear receptors. Curr Opin Biotechnol 6: 582–589

    Article  CAS  Google Scholar 

  31. Mangelsdorf DJ, Evans RM (1995) The RXR heterodimers and orphan receptors. Cell 83: 841–850

    Article  PubMed  CAS  Google Scholar 

  32. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P et al (1995) The nuclear receptor superfamily—the 2nd decade. Cell 83: 835–839

    Article  PubMed  CAS  Google Scholar 

  33. Leid M, Kastner P, Chambon P (1992) Multiplicity generates diversity in the retinoic acid signalling pathways. Trends Biochem Sci 17: 427–433

    Article  PubMed  CAS  Google Scholar 

  34. Leid M, Kastner P, Lyons R, Nakshatri H, Saunders M, Zacharewski T, Chen J-Y, Staub A, Gamier J-M, Mader S et al (1992) Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. Cell 68: 377–395

    Article  PubMed  CAS  Google Scholar 

  35. Zelent A (1995) Molecular mechanisms of retinoid action. In:L Degos, DR Parkinson (eds): Retinoids in Oncology. Springer-Verlag, Heidelberg, 3–25

    Chapter  Google Scholar 

  36. Mangelsdorf DJ, Borgmeyer U, Heyman RA, Zhou JY, Ong ES, Oro AE, Kakizuka A, Evans RM (1992) Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Gene Develop 6: 329–344

    Article  CAS  Google Scholar 

  37. Nagpal S, Saunders M, Kastner P, Durand B, Nakshatri H, Chambon P (1992) Promoter context-and response element-dependent specificity of the transcriptional activation and modulating functions of retinoic acid receptors. Cell 70: 1007–1019

    Article  PubMed  CAS  Google Scholar 

  38. Tora L, Gronemeyer H, Turcotte B, Gaub MP, Chambon P (1988) The N-terminal region of the chicken progesterone receptor specifies target gene activation. Nature 333: 185–188

    Article  PubMed  CAS  Google Scholar 

  39. Tasset D, Tora L, Fromental C, Scheer E, Chambon P (1990) Distinct classes of transcriptional activating domains function by different mechanisms. Cell 62: 1177–1187

    Article  PubMed  CAS  Google Scholar 

  40. Baur EV, Zechel C, Heery D, Heine MJS, Gamier JM, Vivat V, Ledouarin B, Gronemeyer H, Chambon P, Losson R (1996) Differential ligand-dependent interactions between the AF-2 activating domain of nuclear receptors and the putative transcriptional intermediary factors mSUG1 and TIF1. EMBO J 15: 110–124

    Google Scholar 

  41. Kamei Y, Xu L, Heinzel T, Torchia J, Kurokawa R, Gloss B, Lin SC, Heyman RA, Rose DW, Glass CK et al (1996) A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell 85: 403–414

    Article  PubMed  CAS  Google Scholar 

  42. Le Douarin B, Zechel C, Gamier JM, Lutz Y, Tora L, Pierrat B, Heery D, Gronemeyer H, Chambon P, Losson R (1995) The N-terminal part of TIF1, a putative mediator of the ligand-dependent activation function (AF-2) of nuclear receptors, is fused to B-Raf in the oncogenic protein T18. EMBO J 14: 2020–2033

    PubMed  Google Scholar 

  43. Halachmi S, Marden E, Martin G, MacKay H, Abbondanza C, Brown M (1994) Estrogen receptor-associated proteins: Possible mediators of hormone induced transcription. Science 264: 1455–1458

    Article  PubMed  CAS  Google Scholar 

  44. Voegel JJ, Heine MJS, Zechel C, Chambon P, Gronemeyer H (1996) TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors. EMBO J 15: 3667–3675

    PubMed  CAS  Google Scholar 

  45. Onate SA, Tsai SY, Tsai MJ, Omalley BW (1995) Sequence and characterization of a coactivator for the steroid-hormone receptor superfamily. Science 270: 1354–1357

    Article  PubMed  CAS  Google Scholar 

  46. Spencer TE, Jenster G, Burcin MM, Allis CD, Zhou J, Mizzen CA, McKenna NJ, Onate SA, Tsai SY, Tsai M-J et al (1997) Steroid receptor coactivator-1 is a histone acetyltransferase. Nature 389: 194–198

    Article  PubMed  CAS  Google Scholar 

  47. Horlein AJ, Naar AM, Heinzel T, Torchia J, Gloss B, Kurokawa R, Ryan A, Kamei Y, Soderstrom M, Glass CK et al (1995) Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature 377: 397–404

    Article  PubMed  CAS  Google Scholar 

  48. Chen JD, Evans RM (1995) A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature 377: 454–457

    Article  PubMed  CAS  Google Scholar 

  49. Alland L, Muhle R, Hou HJr, Potes J, Chin L, Schreiber-Agus N, DePinho RA (1997) Role for N-CoR and histone deacetylase in Sin3-mediated transcriptional repression. Nature 387: 49–55

    Article  PubMed  CAS  Google Scholar 

  50. Heinzel T, Lavinsky RM, Mullen TM, Soderstrom M, Laherty CD, Torchia J, Yang WM, Brard G, Ngo SD, DavieJr et al (1997) A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature 387: 43–48

    Article  PubMed  CAS  Google Scholar 

  51. Nagy L, Kao HY, Chakravarti D, Lin RJ, Hassig CA, Ayer DE, Schreiber SL, Evans RM (1997) Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase. Cell 89: 373–380

    Article  PubMed  CAS  Google Scholar 

  52. Wang H, Stillman DJ (1990) In vitro regulation of a SIN3-dependent DNA-binding activity by stimulatory and inhibitory factors. Proc Natl Acad Sci USA 87: 9761–9765

    Article  PubMed  CAS  Google Scholar 

  53. Wang H, Clark I, Nicholson PR, Herskowitz I, Stillman DJ (1990) The Saccharomyces cerevisiae SIN3 gene, a negative regulator of HO, contains four paired amphipathic helix motifs. Mol Cell Biol 10: 5927–5936

    PubMed  CAS  Google Scholar 

  54. Wang H, Stillman DJ (1993) Transcriptional repression in Saccharomyces cerevisiae by a SIN3-LexA fusion protein. Mol Cell Biol 13: 1805–1814

    PubMed  CAS  Google Scholar 

  55. Taunton J, Hassig CA, Schreiber SL (1996) A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science 272: 408–411

    Article  PubMed  CAS  Google Scholar 

  56. Laherty CD, Yang WM, Sun JM, DavieJr, Seto E, Eisenman RN (1997) Histone deacetylases associated with the mSin3 corepressor mediate Mad transcriptional repression. Cell 89: 349–356

    Article  PubMed  CAS  Google Scholar 

  57. Hassig CA, Fleischer TC, Billin AN, Schreiber SL, Ayer DE (1997) Histone deacetylase activity is required for full transcriptional repression by mSin3A. Cell 89: 341–347

    Article  PubMed  CAS  Google Scholar 

  58. Luo RX, Postigo AA, Dean DC (1998) Rb interacts with histone deacetylase to repress transcription. Cell 92: 463–473

    Article  PubMed  CAS  Google Scholar 

  59. Brehm A, Miska EA, McCance DJ, Reid JL, Bannister AJ, Kouzarides T (1998) Retinoblastoma protein recruits histone deacetylase to repress transcription. Nature 391: 597–601

    Article  PubMed  CAS  Google Scholar 

  60. Magnaghi-Jaulin L, Groisman R, Naguibneva I, Robin P, Lorain S, Le-Villain J, Troalen F, Trouche D, HarelBellan A (1998) Retinoblastoma protein represses transcription by recruiting a histone deacetylase. Nature 391: 601–605

    Article  PubMed  CAS  Google Scholar 

  61. Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, Bird A (1998) Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393: 386–389

    Article  PubMed  CAS  Google Scholar 

  62. Lotan R (1980) Effects of vitamin A and its analogs (retinoids) on normal and neoplastic cells. Biochim Biophys Acta 605: 33–91

    PubMed  CAS  Google Scholar 

  63. Roberts AB, Sporn MB (1984) Cellular biology and biochemistry of the retinoids. In:MB Sporn, AB Roberts, DS Goodman (eds): The Retinoids. Academic Press, Orlando, 209–284

    Google Scholar 

  64. Hodges RE, Sauberlich HE, Canham JE, Wallace DL, Rucker RB, Mejia LA, Mohanram M (1978) Hematopoictic studies in vitamin A deficiency. Amer J Clin Nutr 31: 876–885

    PubMed  CAS  Google Scholar 

  65. Amatruda T, Koeffler H (1986) Retinoids and cells of the hematopoietic system. In:M Sherman (ed.): Retinoids and Cell Differentiation. CRC Press, Boca Raton, 79–103

    Google Scholar 

  66. Ross AC (1992) Vitamin A status: relationship to immunity and the antibody response. Proc Soc Exp Biol Med 200: 303–320

    PubMed  CAS  Google Scholar 

  67. Tsai S, Collins SJ (1993) A dominant negative retinoic acid receptor blocks neutrophil differentiation at the promyelocyte stage. Proc Natl Acad Sci USA 90: 7153–7157

    Article  PubMed  CAS  Google Scholar 

  68. Tsai S, Bartelmez S, Heyman R, Damm K, Evans R, Collins SJ (1992) A mutated retinoic acid receptor-a exhibiting dominant-negative activity alters the lineage development of a multipotent hematopoietic cell line. Gene Develop 6: 2258–2269

    Article  CAS  Google Scholar 

  69. Mehta K, McQueen T, Manshouri T, Andreeff M, Collins S, Albitar M (1997) Involvement of retinoic acid receptor-a-mediated signalling pathway in induction of CD38 cell-surface antigen. Blood 89: 3607–3614

    PubMed  CAS  Google Scholar 

  70. Zelent A, Zhu J, Lanotte M, Gallagher R, Waxman S, Heyworth CM, Enver T (1997) Differential expression of retinoid receptors during multilineage differentiation of haematopoietic progenitor cells-role of the RARa2 isoform in normal granulopoiesis and leukaemia. Blood 90: 186

    Google Scholar 

  71. Chen JY, Clifford J, Zusi C, Starrett J, Tortolani D, Ostrowski J, Reczek PR, Chambon P, Gronemeyer H (1996) Two distinct actions of retinoid-receptor ligands. Nature 382: 819–822

    Article  PubMed  CAS  Google Scholar 

  72. Bishop JM (1986) Oncogenes as hormone receptors. Nature 321: 112–113

    Article  PubMed  CAS  Google Scholar 

  73. Green S, Chambon P (1986) A superfamily of potentially oncogenic hormone receptors. Nature 324: 615–617.

    Article  PubMed  CAS  Google Scholar 

  74. Zenke M, Munoz A, Sap J, Vennstrom B, Beug H (1990) v-erbA oncogene activation entails the loss of hormone-dependent regulator activity of c-erbA. Cell 61: 1035–1049

    CAS  Google Scholar 

  75. Damm K, Thompson CC, Evans RM (1989) Protein encoded by v-erbA functions as a thyroid-hormone receptor antagonist. Nature 339: 593–597

    Article  PubMed  CAS  Google Scholar 

  76. Sharif M, Privalsky ML (1991) v-erbA oncogene function in neoplasia correlates with its ability to repress retinoic acid receptor action. Cell 66: 885–893

    CAS  Google Scholar 

  77. Desbois C, Aubert D, Legrand C, Pain B, Samarut J (1991) A novel mechanism of action for v-ErbA: abrogation of the inactivation of transcription factor AP-1 by retinoic acid and thyroid hormone receptors. Cell 67:731–740

    Article  PubMed  CAS  Google Scholar 

  78. Houle B, Rochette-Egly C, Bradley WEC (1993) Tumor-suppressive effect of the retinoic acid receptor (3 in human epidermoid lung cancer cells. Proc Natl Acad Sci USA 90: 985–989

    Article  PubMed  CAS  Google Scholar 

  79. Gebert JF, Moghal N, Frangioni JV, Sugarbaker DJ, Neel BG (1991) High frequency of retinoic acid receptor 13 abnormalities in human lung cancer. Oncogene 6: 1859–1868

    PubMed  CAS  Google Scholar 

  80. de The H, Marchio A, Tiollais P, Dejean A (1987) A novel steroid thyroid hormone receptor-related gene inappropriately expressed in human hepato-cellular carcinoma. Nature 330: 667–670

    Article  PubMed  Google Scholar 

  81. Garcia M, de The H, Tiollais P, Samarut J, Dejean A (1993) A hepatitis B virus pre-S-retinoic acid receptor 13 chimera transforms erythrocytic progenitor cells in vitro. Proc Nall Acad Sci USA 90: 89–93

    Article  CAS  Google Scholar 

  82. Kakizuka A, Miller WH, Umesono K, Warrell RP, Frankel SR, Murty VVVS, Dimitrovsky E, Evans RM (1991) Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RARa with a novel putative transcription factor, PML. Cell 66: 663–674

    Article  PubMed  CAS  Google Scholar 

  83. de The H, Lavau C, Marchio A, Chomienne C, Degos L, Dejean A (1991) The PLM-RARa fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. Cell 66: 675–684

    Article  PubMed  Google Scholar 

  84. Goddard AD, Borrow J, Freemont P, Solomon E (1991) Characterization of a zinc finger gene disrupted by the t(15;17) in acute promyelocytic leukemia. Science 254: 1371–1374

    Article  PubMed  CAS  Google Scholar 

  85. Pandolfi PP, Grignani F, Alcalay M, Mencarelli A, Biondi A, Lo Coco F, Grignani F, Pelicci PG (1991) Structure and origin of the acute promyelocytic leukemia myl/RARa cDNA and characterization of its retinoid-binding and transactivation properties. Oncogene 6: 1285–1292

    PubMed  CAS  Google Scholar 

  86. Kastner P, Perez A, Lutz Y, Rochette-Egly C, Gaub M-P, Durand B, Lanotte M, Berger R, Chambon P (1992) Structure, localization and transcriptional properties of two classes of retinoic acid receptor a fusion proteins in acute promyelocytic leukemia (APL): structural similarities with a new family of oncoproteins. EMBO J 11: 629–642

    PubMed  CAS  Google Scholar 

  87. He L-Z, Guidez F, Tribioli C, Peruzzi D, Ruthardt M, Zelent A, Pandolfi PP (1998) Distinct interactions of PML-RARa with transcriptional co-repressors determine differential responses to retinoic acid in APL. Nat Genet 18: 126–135

    Article  PubMed  CAS  Google Scholar 

  88. He LZ, Tribioli C, Rivi R, Peruzzi D, Pelicci PG, Soares V, Cattoretti G, Pandolfi PP (1997) Acute leukemia with promyelocytic features in PML/RARa transgenic mice. Proc Natl Acad Sci USA 94: 5302–5307

    Article  PubMed  CAS  Google Scholar 

  89. Brown D, Kogan S, Lagasse E, Weissman I, Alcalay M, Pelicci PG, Atwater S, Bishop JM (1997) A PMLRARa transgene initiates murine acute promyelocytic leukemia. Proc Natl Acad Sci USA 94: 2551–2556

    Article  PubMed  CAS  Google Scholar 

  90. Early E, Moore MA, Kakizuka A, Nason Burchenal K, Martin P, Evans RM, Dmitrovsky E (1996) Transgenic expression of PML-RARa impairs myelopoiesis. Proc Nall Acad Sci USA 93: 7900–7904

    Article  CAS  Google Scholar 

  91. Grignani F, Testa U, Rogaia D, Ferrucci PF, Samoggia P, Pinto A, Aldinucci D, Gelmetti V, Fagioli M, Alcalay M et al (1996) Effects on differentiation by the promyelocytic leukemia PMLRARa protein depend on the fusion of the PML protein dimerization and RARa DNA-binding domains. EMBO J 15: 4949–4958

    PubMed  CAS  Google Scholar 

  92. Raelson JV, Nervi C, Rosenauer A, Benedetti L, Monczak Y, Pearson M, Pelicci PG, Miller WH (1996) The PML/RARa oncoprotein is a direct molecular target of retinoic acid in acute promyelocytic leukemia cells. Blood 88: 2826–2832

    PubMed  CAS  Google Scholar 

  93. Koken MHM, Puvion-Dutilleul F, Guillemin MC, Viron A, Linares-Cruz G, Stuurman N, de Jong L, Szostecki C, Clavo F, Chomienne C et al (1994) The t(15;17) translocation alters a nuclear body in a retinoic acid-reversible fashion. EMBO J 13: 1073–1083

    PubMed  CAS  Google Scholar 

  94. Weis K, Rambaud S, Lavau C, Jansen J, Carvalho T, Carmo-Fonseca M, Lamond A, Dejean A (1994) Retinoic acid regulates aberrant nuclear localization of PML-RARa in acute promyelocytic leukemia cells. Cell 76: 345–356

    Article  PubMed  CAS  Google Scholar 

  95. Dyck JA, Maul GG, Miller WHJr, Chen JD, Kakizuka A, Evans RM (1994) A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein. Cell 76: 333–343

    Article  PubMed  CAS  Google Scholar 

  96. Redner RL, Rush EA, Faas S, Rudert WA, Corey SJ (1996) The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion. Blood 87: 882–886

    PubMed  CAS  Google Scholar 

  97. Chen Z, Brand NJ, Chen A, Chen S-J, Tong J-H, Wang Z-Y, Waxman S, Zelent A (1993) Fusion between a novel Kruppel-like zinc finger gene and the retinoic acid receptor-a locus due to a variant t(11;17) translocation associated with acute promeylocytic leukaemia. EMBO J 12: 1161–1167

    PubMed  CAS  Google Scholar 

  98. Chen S-J, Zelent A, Tong J-H, Yu H-Q, Wang Z-Y, Derre J, Berger R, Waxman S, Chen Z (1993) Rearrangements of the retinoic acid receptor a and promyelocytic leukemia zinc finger genes resulting from t(11;17)(g23;g21) in a patient with acute promyelocytic leukemia. J Clin Invest 91: 2260–2267

    Article  PubMed  CAS  Google Scholar 

  99. Wells RA, Catzavclos C, Kamel-Reid S (1997) Fusion of retinoic acid receptor a to NuMA, the mitotic apparatus protein, by a variant translocation in acute promyelocytic leukaemia. Nat Genet 17: 109–113

    Article  PubMed  CAS  Google Scholar 

  100. Guidez F, Huang W, Tong J-H, Dubois C, Balitrand N, Waxman S, Michaux JL, Martiat P, Degos L, Chen Z et al (1994) Poor response to all-trans retinoic acid therapy in a t(11;17) PLZF/RARa patient. Leukemia 8: 312–317

    PubMed  CAS  Google Scholar 

  101. Licht JD, Chomienne C, Goy A, Chen A, Scott AA, Head DR, Michaux JL, DeBlasio A, Miller WJr, Zelenetz AD et al (1995) Clinical and molecular characterization of a rare syndrom of acute promyelocytic leukemia associated with translocation (11;17). Blood 85: 1083–1094

    PubMed  CAS  Google Scholar 

  102. Kerckaert J-P, Deweindt C, Tilly H, Quief S, Lecocq G, Bastard C (1993) LAZ3 a novel zinc-finger encod-ing gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas. Nat Genet 5: 66–70

    CAS  Google Scholar 

  103. Ye BH, Lista F, Lo Coco F, Knowles DM, Offit K, Chaganti RSK, Dalla-Favera R (1993) Alterations of a zinc finger-encoding gene BCL-6 in diffuse large-cell lymphoma. Science 262: 747–750

    Article  PubMed  CAS  Google Scholar 

  104. Miki T, Kawamata N, Hirosawa S, Aoki N (1994) Gene involved in the 3q27 translocation associated with B-cell lymphoma BCL5 encodes a Kruppel-like zinc-finger protein. Blood 83: 26–32

    PubMed  CAS  Google Scholar 

  105. Baron BW, Nucifora G, McCabe N, Espinosa RI, LeBeau MM, McKeithan TW (1993) Identification of the gene associated with the recurring chromosomal translocation t(3;14)q27;q23) and t(3;22)(g27;g11) in B-cell lymphomas. Proc Natl Acad Sci USA 90: 5262–5266

    Article  PubMed  CAS  Google Scholar 

  106. Dhordain P, Albagli O, Lin JN, Ansieau S, Quief S, Leutz A, Kerckaert J-P, Evans RM, Leprince D (1997) Corepressor SMRT binds the BTB/POZ repressing domain of the LAZ3/BCL6 oncoprotein. Proc Natl Acad Sci USA 94: 10762–10767

    Article  PubMed  CAS  Google Scholar 

  107. Hong SH, David G, Wong CW, Dejean A, Privalsky ML (1997) SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor a (RARa) and PLZF-RARot oncoproteins associated with acute promyelocytic leukemia. Proc Natl Acad Sci USA 94: 9028–9033

    Article  PubMed  CAS  Google Scholar 

  108. Guidez F, Ivins S, Zhu J, Soderstrom M, Waxman S, Zelent A (1998) Reduced retinoic acid-sensitivities of nuclear receptor co-repressor binding to PML- and PLZF-RARa underlie molecular pathogenesis and treatment of acute promyelocytic leukemia. Blood 91: 2634–2642

    PubMed  CAS  Google Scholar 

  109. Grignani F, DeMatteis S, Nervi C, Tomassoni L, Gelmetti V, Cioce M, Fanelli M, Ruthardt M, Ferrara FF, Zamir I et al (1998) Fusion proteins of the retinoic acid receptor-a recruit histone deacetylase in promyelocytic leukaemia. Nature 391: 815–818

    Article  PubMed  CAS  Google Scholar 

  110. Lin R, Nagy L, Inoue S, Shao W, MillerJr, W, Evans R (1998) Role of histone deacetylase complex in acute promyelocytic lekaemia. Nature 391: 811–814

    Article  PubMed  CAS  Google Scholar 

  111. David G, Alland L, Hong S-H, Wong C-W, DePinho R, Dejean A (1998) Histone deacetylase associated with mSin3A mediates repression by the promyelocytic leukemia-associated PLZF protein. Oncogene 16: 2549–2556

    Article  PubMed  CAS  Google Scholar 

  112. Koken MHM, Reid A, Quignon F, Chelbi-Alix MK, Davies JM, Kabarowski JHS, Zhu J, Dong S, Chen S-J, Chen Z et al (1997) Leukemia associated retinoic acid receptor a fusion partners, PML and PLZF, heterodimerize and colocalize to nuclear bodies. Proc Natl Acad Sci USA 94: 10255–10260

    Article  PubMed  CAS  Google Scholar 

  113. Redner R, Rush E, Schlesinger K, Pollock S, Watkins S (1997) The t(5;17) APL fusion protein NPM-RAR does not alter PML localization. Blood 90: 1431

    Google Scholar 

  114. Ruthardt M, Orleth A, Tomassoni L, Puccetti E, Riganelli D, Alcalay M, Mannucci R, Nicoletti I, Grignani F, Fagioli M et al (1998) The acute promyelocytic leukaemia specific PML and PLZF proteins localize to adjacent and functionally distinct nuclear bodies. Oncogene 16: 1945–1953

    Article  PubMed  CAS  Google Scholar 

  115. Perez A, Kastner P, Sethi S, Lutz Y, Reibel C, Chambon P (1993) PML/RAR homodimers: distinct DNA binding properties and heteromeric interactions with RXR. EMBO J 12: 3171–3182

    PubMed  CAS  Google Scholar 

  116. Licht JD, Shaknovich R, English MA, Melnick A, Li J-Y, Reddy JC, Dong S, Chen S-J, Zelent A, Waxman S (1996) Reduced and altered DNA-binding and transcriptional properties of the PLZF-retinoic acid receptor-a chimera generated in t(11;17)-associated acute promyelocytic leukemia. Oncogene 12: 323–336

    PubMed  CAS  Google Scholar 

  117. Dong S, Zhu J, Reid A, Strutt P, Guidez F, Zhong H-J, Wang Z-Y, Licht J, Waxman S, Chomienne C et al (1996) Amino-terminal protein-protein interaction motif (POZ-domain) is responsible for activities of the promyelocytic leukemia zinc finger-retinoic acid receptor-a fusion protein. Proc Natl Acad Sci USA 93: 3624–3629

    Article  PubMed  CAS  Google Scholar 

  118. Chen Z, Guidez F, Rousselot P, Agadir A, Chen S-J, Wang Z-Y, Degos L, Zelent A, Waxman S, Chomienne C (1994) PLZF-RARa fusion proteins generated from the variant t(11;17)(g23;21) translocation in acute promyelocytic leukemia inhibit ligand-dependent transactivation of wild-type retinoic acid receptors. Proc Natl Acad Sci USA 91: 1178–1182

    Article  PubMed  CAS  Google Scholar 

  119. Warrell RPJr, He LZ, Richon V, Calleja E, Pandolfi PP (1998) Therapeutic targeting of transcription in acute promyelocytic leukemia by use of an inhibitor of histone deacetylase. J Nat Cancer Inst 90: 1621–1625

    Article  PubMed  CAS  Google Scholar 

  120. Ding W, Li YP, Nobile LM, Grills G, Carrera I, Paietta E, Tallman MS, Wiemik PH, Gallagher RE (1998) Leukemic cellular retinoic acid resistance and missense mutations in the PML-RARa fusion gene after relapse of acute promyelocytic leukemia from treatment with all-trans retinoic acid and intensive chemotherapy [In Process Citation]. Blood 92: 1172–1183

    PubMed  CAS  Google Scholar 

  121. Nagy L, Thomazy VA, Shipley GL, Fesus L, Lamph W, Heyman RA, Chandraratna RA, Davies PJ (1995) Activation of retinoid X receptors induces apoptosis in HL-60 cell lines. Mol Cell Biol 15: 3540–3551

    PubMed  CAS  Google Scholar 

  122. Smeland EB, Rusten L, Jacobsen SE, Skrede B, Blomhoff R, Wang MY, Funderud S, Kvalheim G, Blomhoff HK (1994) All-trans retinoic acid directly inhibits granulocyte colony-stimulating factor-induced proliferation of CD34+ human hematopoietic progenitor cells. Blood 84: 2940–2945

    CAS  Google Scholar 

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  1. Leukaemia Research Fund Centre at the Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK

    F. Guidez & A. Zelent

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  1. F. Guidez
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  1. Cattedra di Chimica Biologica, Istituto di Farmacologia e Farmacognosia, UniversitĂ  di Palermo, Via Forlanini 1, Palermo, I-90134, Italy

    Maria A. Livrea

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Guidez, F., Zelent, A. (2000). Retinoic acid receptors in normal and neoplastic haematopoietic cells. In: Livrea, M.A. (eds) Vitamin A and Retinoids: An Update of Biological Aspects and Clinical Applications. MCBU Molecular and Cell Biology Updates. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8454-9_11

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  • DOI: https://doi.org/10.1007/978-3-0348-8454-9_11

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