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The theory of APL


Acute promyelocytic leukemia (APL) is associated with reciprocal and balanced chromosomal translocations always involving the Retinoic Acid Receptor α (RARα) gene on chromosome 17 and variable partner genes (X genes) on distinct chromosomes. RARα fuses to the PML gene in the vast majority of APL cases, and in a few cases to the PLZF, NPM, NuMA and STAT5b genes. As a consequence, X-RARα and RARα-X fusion genes are generated encoding aberrant fusion proteins that can interfere with X and/or RARα function. Here we will review the relevant conclusions and the open questions that stem from a decade of in vivo analysis of APL pathogenesis in the mouse in transgenic and knock-out models.

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  • Albertson DG, Ylstra B, Segraves R, Collins C, Dairkee SH, Kowbel D, Kuo WL, Gray JW, Pinkel D . 2000 Nature Genet. 25: 144–146

  • Arnould C, Philippe C, Bourdon V, Gregoire MJ, Berger R, Jonveaux P . 1999 Hum. Mol. Genet. 8: 1741–1749

  • Barna M, Hawe N, Niswander L, Pandolfi PP . 2000 Nature Genet. 25: 166–172

  • Bardwell VJ, Treisman R . 1994 Genes Dev. 8: 1664–1677

  • Brown D, Kogan S, Lagasse E, Weissman I, Alcalay M, Pelicci PG, Atwater S, Bishop JM . 1997 Proc. Natl. Acad. Sci. USA 94: 2551–2556

  • Casini T, Pelicci PG . 1999 Oncogene 18: 3235–3243

  • Chen Z, Brand NJ, Chen A, Chen SJ, Tong JH, Wang ZY, Waxman S, Zelent A . 1993 EMBO J. 12: 1161–1167

  • de The H, Lavau C, Marchio A, Chomienne C, Degos L, Dejean A . 1991 Cell 66: 675–684

  • Early E, Moore MA, Kakizuka A, Nason-Burchenal K, Martin P, Evans RM, Dmitrovsky E . 1996 Proc. Natl. Acad. Sci. USA 93: 7900–7904

  • Ferbeyre G, de Stanchina E, Querido E, Baptiste N, Prives C, Lowe SW . 2000 Genes Dev. 14: 2015–2027

  • Fogal V, Gostissa M, Sandy P, Zacvchi P, Sternsdorf K, Jensen K, Pandolfi PP, Will H, Schneider C, Del Sal G . 2000 EMBO J. 6: 185–195

  • Goddard AD, Borrow J, Freemont PS, Solomon E . 1991 Science 254: 1371–1374

  • Grignani F, De Matteis S, Nervi C, Tomassoni L, Gelmetti V, Cioce M, Fanelli M, Ruthardt M, Ferrara FF, Zamir I, Seiser C, Lazar MA, Minucci S, Pelicci PG . 1998 Nature 391: 815–818

  • Grisolano JL, Wesselschmidt RL, Pelicci PG, Ley TJ . 1997 Blood 89: 376–387

  • Guo A, Salomoni P, Juo J, Shih A, Zhong S, Gu W, Pandolfi PP . 2000 Nature Cell Biol. 2: 730–736

  • He LZ, Tribioli C, Rivi R, Peruzzi D, Pelicci PG, Soares V, Cattoretti G, Pandolfi PP . 1997 Proc. Natl. Acad. Sci. USA 94: 5302–5307

  • He LZ, Guidez F, Tribioli C, Peruzzi D, Ruthardt M, Zelent A, Pandolfi PP . 1998 Nature Genet. 18: 126–135

  • He LZ, Bhaumik M, Tribioli C, Rego EM, Ivins S, Zelent A, Pandolfi PP . 2000 Mol. Cell 6: 1131–1141

  • Kakizuka A, Miller Jr WH, Umesono K, Warrell Jr RP, Frankel SR, Murty VV, Dmitrovsky E, Evans RM . 1991 Cell 66: 663–674

  • Kogan SC, Hong SH, Shultz DB, Privalsky ML, Bishop JM . 2000 Blood 95: 1541–1550

  • Koken MH, Reid A, Quignon F, Chelbi-Alix MK, Davies JM, Kabarowski JH, Zhu J, Dong S, Chen S, Chen Z, Tan CC, Licht J, Waxman S, de The H, Zelent A . 1997 Proc. Natl. Acad. Sci. USA 94: 10255–10260

  • Koken MH, Daniel MT, Gianni M, Zelent A, Licht J, Buzyn A, Minard P, Degos L, Varet B, de The H . 1999 Oncogene 18: 1113–1118

  • Lagasse E, Weissman IL . 1994 J. Exp. Med. 179: 1047–1052

  • Lallemand-Breitenbach V, Guillemin MC, Janin A, Daniel MT, Degos L, Kogan SC, Bishop JM, de The H . 1999 J. Exp. Med. 189: 1043–1052

  • Licht JD, Chomienne C, Goy A, Chen A, Scott AA, Head DR, Michaux JL, Wu Y, DeBlasio A, Miller Jr WH . 1995 Blood 85: 1083–1094

  • Lin RJ, Nagy L, Inoue S, Shao W, Miller Jr WH, Evans RM . 1998 Nature 391: 811–814

  • Liu QR, Chan PK . 1991 Eur. J. Biochem. 200: 715–721

  • Liu M, Iavarone A, Freedman LP . 1996 J. Biol. Chem. 271: 31723–31728

  • Liu TX, Zhang JW, Tao J, Zhang RB, Zhang QH, Zhao CJ, Tong JH, Lanotte M, Waxman S, Chen SJ, Mao M, Hu GX, Zhu L, Chen Z . 2000 Blood 96: 1496–1504

  • Pandolfi PP, Grignani F. Alcalay M, Mencarelli A, Biondi A, LoCoco F, Pelicci PG . 1991 Oncogene 6: 1285–1292

  • Pandolfi PP . 2001 Oncogene 20: 3116–3127

  • Pearson M, Carbone R, Sebastiani C, Cioce M, Fagioli M, Saito S, Higashimoto Y, Appella E, Minucci S, Pandolfi PP, Pelicci PG . 2000 Nature 406: 207–210

  • Perez A, Kastner P, Sethi S, Lutz Y, Reibel C, Chambon P . 1993 EMBO J. 12: 3171–3182

  • Pollock JL, Westervelt P, Kurichety AK, Pelicci PG, Grisolano JL, Ley TJ . 1999 Proc. Natl. Acad. Sci. USA 96: 15103–15108

  • Quignon F, De Bels F, Koken M, Feunteun J, Ameisen JC, de The H . 1998 Nature Genet. 20: 259–265

  • Redner RL, Rush EA, Faas S, Rudert WA, Corey SJ . 1996 Blood 87: 882–886

  • Rego EM, He LZ, Warrell Jr RP, Wang ZG, Pandolfi PP . 2000 Proc. Natl. Acad. Sci. USA 97: 10173–10178

  • Rego EM, Wang ZG, Peruzzi D, He LZ, Cordon-Cardo C, Pandolfi PP . 2001 J. Exp. Med. 193: 521–529

  • Ruthardt M, Testa U, Nervi C, Ferrucci PF, Grignani F, Puccetti E, Grignani F, Peschle C, Pelicci PG . 1997 Mol. Cell. Biol. 17: 4859–4869

  • Torii S, Egan DA, Evans RA, Reed JC . 1999 EMBO J. 18: 6037–6049

  • Wang ZG, Delva L, Gaboli M, Rivi R, Giorgio M, Cordon-Cardo C, Grosveld F, Pandolfi PP . 1998a Science 279: 1547–1451

  • Wang ZG, Ruggero D, Ronchetti S, Zhong S, Gaboli M, Rivi R, Pandolfi PP . 1998b Nature Genet. 20: 266–272

  • Wells RA, Catzavelos C, Kamel-Reid S . 1997 Nature Genet. 17: 109–113

  • Zhong S, Delva L, Rachez C, Cenciarelli C, Gandini D, Zhang H, Kalantry S, Freedman LP, Pandolfi PP . 1999a Nature Genet. 23: 287–295

  • Zhong S, Hu P, Ye TZ, Stan R, Ellis NA, Pandolfi PP . 1999b Oncogene 18: 7941–7947

  • Zhong S, Salomoni P, Ronchetti S, Guo A, Ruggero D, Pandolfi PP . 2000 J. Exp. Med. 191: 631–640

  • Zimonjic DB, Pollock JL, Westervelt P, Popescu NC, Ley TJ . 2000 Proc. Natl. Acad. Sci. USA 97: 13306–13311

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This work is supported by the NCI, the De Witt Wallace Fund for Memorial Sloan-Kettering Cancer Center, the Mouse Model of Human Cancer Consortium (MMHCC) and NIH Grants to PP Pandolfi and the Lymphoma & Leukemia Society of which PP Pandolfi is a Scholar. Finally, we are indebted to all the past and present members of the laboratory of Molecular and Developmental Biology (MADB) at the Memorial Sloan-Kettering Cancer Center, working on APL and related subjects.

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Correspondence to Pier Paolo Pandolfi.

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Piazza, F., Gurrieri, C. & Pandolfi, P. The theory of APL. Oncogene 20, 7216–7222 (2001).

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  • APL
  • transgenic mice
  • KO mice
  • animal models
  • tumor metamorphosers

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