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  • Oncogenomics
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MLL5, a homolog of Drosophila trithorax located within a segment of chromosome band 7q22 implicated in myeloid leukemia

Abstract

Proteins encoded by Polycomb and Trithorax-group (Pc-G and Trx-G) genes regulate developmental fates by maintaining or repressing HOX gene expression, respectively. In a search for candidate myeloid leukemia tumor suppressor genes from a 2.5 Mb commonly-deleted segment within chromosome band 7q22, we identified a novel human Trithorax (Trx) family member named MLL5. Trx-G genes encode proteins that modulate transcriptional programs through protein–protein interactions that are mediated by PHD and SET domains, and by binding to DNA via A-T hooks and methyltransferase homology motifs. MLL5 is a homolog of the Drosophila gene CG9007; it encodes a 6.5 kb mRNA that is expressed widely. MLL5 includes a SET domain and a single PHD finger, but lacks A-T hooks and methyltransferase homology domains that are found in MLL. The leukemia cell line RCV-ACV-A carries a heterozygous missense mutation within the PHD domain; however, no mutations within the MLL5 coding region were detected in primary leukemias. MLL5 is a novel mammalian Trx-G gene that might modulate transcription by protein association.

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References

  • Alkema MJ, Jacobs H, van Lohuizen M, Berns A . 1997 Oncogene 15: 899–910

  • Allen RJ, Smith SD, Moldwin RL, Lu MM, Giordano L, Vignon C, Suto Y, Harden A, Tomek R, Veldman T, Ried T, Larson RA, Le Beau MM, Rowley JD, Zeleznik-Le N . 1998 Leukemia 12: 1119–1127

  • Baylin SB, Belinsky SA, Herman JG . 2000 J. Natl. Cancer Inst. 92: 1460–1461

  • Borrow J, Shearman AM, Stanton Jr VP, Becher R, Collins T, Williams AJ, Dube I, Katz F, Kwong YL, Morris C, Ohyashiki K, Toyama K, Rowley J, Housman DE . 1996 Nat. Genet. 12: 159–167

  • Canaani E, Nowell PC, Croce CM . 1995 Adv. Cancer Res. 66: 213–234

  • Corral J, Lavenir I, Impey H, Warren AJ, Forster A, Larson TA, Bell S, McKenzie AN, King G, Rabbitts TH . 1996 Cell 85: 853–861

  • Dimartino JF, Cleary ML . 1999 Br. J. Haematol. 106: 614–626

  • Dobson CL, Warren AJ, Pannell R, Forster A, Lavenir I, Corral J, Smith AJ, Rabbitts TH . 1999 EMBO J. 18: 3564–3574

  • Gould A . 1997 Curr. Opin. Genet. Dev. 7: 488–494

  • Hanahan D, Weinberg RA . 2000 Cell 100: 57–70

  • Hanson RD, Hess JL, Yu BD, Ernst P, van Lohuizen M, Berns A, van der Lugt NM, Shashikant CS, Ruddle FH, Seto M, Korsmeyer SJ . 1999 Proc. Natl. Acad. Sci. USA 96: 14372–14377

  • Kalra R, Paderanga D, Olson K, Shannon KM . 1994 Blood 84: 3435–3439

  • Kaneko Y, Maseki N, Sakuri M, Shibuya A, Shinohara T, Fujimoto T, Kanno H, Nishikawa A . 1989 Leukemia 3: 36–41

  • Kratz CP, Emerling BM, Donovan S, Laig-Webster M, Taylor BR, Thompson P, Jensen S, Banerjee A, Bonifas J, Makalowski W, Green ED, Le Beau MM, Shannon KM . 2001 Genomics 77: 171–180

  • Lavau C, Du C, Thirman M, Zeleznik-Le N . 2000 EMBO J. 19: 4655–4664

  • Lawrence HJ, Largman C . 1992 Blood 80: 2445–2453

  • Le Beau M, Albain KS, Larson RA, Vardiman J, Davis E, Blough R, Golomb H, Rowley J . 1986 J. Clin. Oncol. 3: 325–345

  • Le Beau MM, Espinosa III R, Davis EM, Eisenbart JD, Larson RA, Green ED . 1996 Blood 88: 1930–1935

  • Lessard J, Baban S, Sauvageau G . 1998 Blood 91: 1216–1224

  • Look A . 1997 Science 278: 1059–1064

  • Luna-Fineman S, Shannon K, Lange BJ . 1995 Blood 85: 1985–1999

  • Luna-Fineman S, Shannon KM, Atwater SK, Davis J, Masterson M, Ortega J, Sanders J, Steinherz P, Weinberg V, Lange BJ . 1999 Blood 93: 459–466

  • Nakamura T, Largaespada DA, Lee MP, Johnson LA, Ohyashiki K, Toyama K, Chen SJ, Willman CL, Chen IM, Feinberg AP, Jenkins NA, Copeland NG, Shaughnessy Jr JD . 1996a Nat. Genet. 12: 154–158

  • Nakamura T, Largaespada DA, Shaughnessy Jr JD, Jenkins NA, Copeland NG . 1996b Nat. Genet. 12: 149–153

  • Rowley JD . 1999 Semin. Hematol. 36: 59–72

  • Rozovskaia T, Rozenblatt-Rosen O, Sedkov Y, Burakov D, Yano T, Nakamura T, Petruck S, Ben-Simchon L, Croce CM, Mazo A, Canaani E . 2000 Oncogene 19: 351–357

  • Rozovskaia T, Tillib S, Smith S, Sedkov Y, Rozenblatt-Rosen O, Petruk S, Yano T, Nakamura T, Ben-Simchon L, Gildea J, Croce CM, Shearn A, Canaani E, Mazo A . 1999 Mol. Cell. Biol. 19: 6441–6447

  • Side L, Taylor B, Cayouette M, Connor E, Thompson P, Luce M, Shannon K . 1997 N. Engl. J. Med. 336: 1713–1720

  • Slany RK, Lavau C, Cleary ML . 1998 Mol. Cell. Biol. 18: 122–129

  • Song WJ, Sullivan MG, Legare RD, Hutchings S, Tan X, Kufrin D, Ratajczak J, Resende IC, Haworth C, Hock R, Loh M, Felix C, Roy DC, Busque L, Kurnit D, Willman C, Gewirtz AM, Speck NA, Bushweller JH, Li FP, Gardiner K, Poncz M, Maris JM, Gilliland DG . 1999 Nat. Genet. 23: 166–175

  • Thirman MJ, Larson RA . 1996 Hematol. Oncol. Clin. North Am. 10: 293–320

  • van Lohuizen M . 1999 Curr. Opin. Genet. Dev. 9: 355–361

  • Yagi H, Deguchi K, Aono A, Tani Y, Kishimoto T, Komori T . 1998 Blood 92: 108–117

  • Yu B, Hess JL, Horning SE, Brown GAJ, Korsmeyer S . 1995 Nature 378: 505–508

  • Zeleznik-Le NJ, Harden AM, Rowley JD . 1994 Proc. Natl. Acad. Sci. USA 91: 10610–10614

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Acknowledgements

This work was supported by PHS grant CA40046 (to MM Le Beau and KM Shannon), by the Frank A Campini Foundation (to KM Shannon), and by a fellowship grant from the Dr Mildred Scheel Stiftung für Krebsforschung (to CP Kratz). These studies were also facilitated by a collaboration with the Children's Oncology Group (Study Number B24), and by the gift of an ABI 7700 Sequence Detection System from Applied Biosystems.

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Correspondence to Kevin M Shannon.

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Emerling, B., Bonifas, J., Kratz, C. et al. MLL5, a homolog of Drosophila trithorax located within a segment of chromosome band 7q22 implicated in myeloid leukemia. Oncogene 21, 4849–4854 (2002). https://doi.org/10.1038/sj.onc.1205615

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