User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies

Primary tabs

Duhoux, François [UCL] Ameye, Geneviève [UCL] Montano Almendras, Carmen Patricia [UCL] Bahloula, Khadija [UCL] Mozziconacci, Marie-Joëlle [Institut Paoli-Calmettes] Michaux, Lucienne [UCL] Latinne, Dominique [UCL] Libouton, Jeanne-Marie [UCL] Demoulin, Jean-Baptiste [UCL] Poirel, Hélène [UCL]

The PRDM16 (1p36) gene is rearranged in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) with t(1;3)(p36;q21), sharing characteristics with AML and MDS with MECOM (3q26.2) translocations. We used fluorescence in situ hybridization to study 39 haematological malignancies with translocations involving PRDM16 to assess the precise breakpoint on 1p36 and the identity of the partner locus. Reverse-transcription polymerase chain reaction (PCR) was performed in selected cases in order to confirm the partner locus. PRDM16 expression studies were performed on bone marrow samples of patients, normal controls and CD34(+) cells using TaqMan real-time quantitative PCR. PRDM16 was rearranged with the RPN1 (3q21) locus in 30 cases and with other loci in nine cases. The diagnosis was AML or MDS in most cases, except for two cases of lymphoid proliferation. We identified novel translocation partners of PRDM16, including the transcription factors ETV6 and IKZF1. Translocations involving PRDM16 lead to its overexpression irrespective of the consequence of the rearrangement (fusion gene or promoter swap). Survival data suggest that patients with AML/MDS and PRDM16 translocations have a poor prognosis despite a simple karyotype and a median age of 65 years. There seems to be an over-representation of late-onset therapy-related myeloid malignancies.

Document type Article de périodique (Journal article) – Article de recherche – Journal Article, Research Support, Non-U.S. Gov't
Access type Accès restreint
Publication date 2012
Language Anglais
Journal information "British Journal of Haematology" - Vol. 156, no. 1, p. 76-88 (2012)
Peer reviewed yes
Publisher Wiley-Blackwell Publishing Ltd. ((United Kingdom) Oxford)
issn 0007-1048
e-issn 1365-2141
Publication status Publié
Affiliation UCL - SSS/DDUV - Institut de Duve
Links
  1. Aguilo F., Avagyan S., Labar A., Sevilla A., Lee D.-F., Kumar P., Lemischka I. R., Zhou B. Y., Snoeck H.-W., Prdm16 is a physiologic regulator of hematopoietic stem cells, 10.1182/blood-2010-08-300145
  2. Barjesteh van Waalwijk van Doorn-Kh S, Low expression of MDS1-EVI1–like-1 (MEL1) and EVI1-like-1 (EL1) genes in favorable-risk acute myeloid leukemia, 10.1016/j.exphem.2003.08.003
  3. Beck A H, Lee C-H, Witten D M, Gleason B C, Edris B, Espinosa I, Zhu S, Li R, Montgomery K D, Marinelli R J, Tibshirani R, Hastie T, Jablons D M, Rubin B P, Fletcher C D, West R B, van de Rijn M, Discovery of molecular subtypes in leiomyosarcoma through integrative molecular profiling, 10.1038/onc.2009.381
  4. Beillard E, Pallisgaard N, van der Velden V H J, Bi W, Dee R, van der Schoot E, Delabesse E, Macintyre E, Gottardi E, Saglio G, Watzinger F, Lion T, van Dongen J J M, Hokland P, Gabert J, Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using ‘real-time’ quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR) – a Europe against cancer program, 10.1038/sj.leu.2403136
  5. Bene, Leukemia, 9, 1783 (1995)
  6. Bertrand P, Bastard C, Maingonnat C, Jardin F, Maisonneuve C, Courel M-N, Ruminy P, Picquenot J-M, Tilly H, Mapping of MYC breakpoints in 8q24 rearrangements involving non-immunoglobulin partners in B-cell lymphomas, 10.1038/sj.leu.2404529
  7. Bjork Bryan C., Turbe-Doan Annick, Prysak Mary, Herron Bruce J., Beier David R., Prdm16 is required for normal palatogenesis in mice, 10.1093/hmg/ddp543
  8. Bloomfield, Blood, 66, 1409 (1985)
  9. Bohlander Stefan K., ETV6: A versatile player in leukemogenesis, 10.1016/j.semcancer.2005.01.008
  10. Breems Dimitri A., Van Putten Wim L.J., De Greef Georgine E., Van Zelderen-Bhola Shama L., Gerssen-Schoorl Klasien B.J., Mellink Clemens H.M., Nieuwint Aggie, Jotterand Martine, Hagemeijer Anne, Beverloo H. Berna, Löwenberg Bob, Monosomal Karyotype in Acute Myeloid Leukemia: A Better Indicator of Poor Prognosis Than a Complex Karyotype, 10.1200/jco.2008.16.0259
  11. Chuikov Sergei, Levi Boaz P., Smith Michael L., Morrison Sean J., Prdm16 promotes stem cell maintenance in multiple tissues, partly by regulating oxidative stress, 10.1038/ncb2101
  12. Couture J.-F., Dirk L. M. A., Brunzelle J. S., Houtz R. L., Trievel R. C., Structural origins for the product specificity of SET domain protein methyltransferases, 10.1073/pnas.0806712105
  13. Deluche Lauréline, Joha Sami, Corm Sélim, Daudignon Agnès, Geffroy Sandrine, Quief Sabine, Villenet Céline, Kerckaert Jean-Pierre, Laï Jean-Luc, Preudhomme Claude, Roche-Lestienne Catherine, Cryptic and partial deletions ofPRDM16andRUNX1without t(1;21)(p36;q22) and/orRUNX1-PRDM16fusion in a case of progressive chronic myeloid leukemia: A complex chromosomal rearrangement of underestimated frequency in disease progression?, 10.1002/gcc.20611
  14. Du Y., Insertional mutagenesis identifies genes that promote the immortalization of primary bone marrow progenitor cells, 10.1182/blood-2005-03-1113
  15. Hazourli Sawcène, Chagnon Pierre, Sauvageau Martin, Fetni Raouf, Busque Lambert, Hébert Josée, Overexpression ofPRDM16 in the presence and absence of theRUNX1/PRDM16 fusion gene in myeloid leukemias, 10.1002/gcc.20370
  16. Horn Kristin H., Warner Dennis R., Pisano Michele, Greene Robert M., PRDM16 expression in the developing mouse embryo, 10.1016/j.acthis.2009.09.006
  17. Hosokawa, Blood, 95, 2719 (2000)
  18. Shaffer, ISCN 2009: An International System for Human Cytogenetic Nomenclature (2009) (2009)
  19. Jiang, Histology and Histopathology, 15, 109 (2000)
  20. Kajimura Shingo, Seale Patrick, Kubota Kazuishi, Lunsford Elaine, Frangioni John V., Gygi Steven P., Spiegelman Bruce M., Initiation of myoblast to brown fat switch by a PRDM16–C/EBP-β transcriptional complex, 10.1038/nature08262
  21. Kim Miran, Lee Han Chu, Tsedensodnom Orkhontuya, Hartley Rochelle, Lim Young-Suk, Yu Eunsil, Merle Philippe, Wands Jack R., Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/β-catenin signaling pathway in hepatocellular carcinoma cells, 10.1016/j.jhep.2007.12.020
  22. Lacy Paige, The role of Rho GTPases and SNAREs in mediator release from granulocytes, 10.1016/j.pharmthera.2005.03.008
  23. Lahortiga Idoya, Agirre Xabier, Belloni Elena, Vázquez Iria, Larrayoz María J, Gasparini Patrizia, Coco Francesco Lo, Pelicci Pier Giuseppe, Calasanz María J, Odero María D, Molecular characterization of a t(1;3)(p36;q21) in a patient with MDS. MEL1 is widely expressed in normal tissues, including bone marrow, and it is not overexpressed in the t(1;3) cells, 10.1038/sj.onc.1206923
  24. Livak Kenneth J., Schmittgen Thomas D., Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method, 10.1006/meth.2001.1262
  25. Lugthart Sanne, Gröschel Stefan, Beverloo H. Berna, Kayser Sabine, Valk Peter J.M., van Zelderen-Bhola Shama Lydia, Jan Ossenkoppele Gert, Vellenga Edo, van den Berg-de Ruiter Eva, Schanz Urs, Verhoef Gregor, Vandenberghe Peter, Ferrant Augustin, Köhne Claus-Henning, Pfreundschuh Michael, Horst Heinz A., Koller Elisabeth, von Lilienfeld-Toal Marie, Bentz Martin, Ganser Arnold, Schlegelberger Brigitte, Jotterand Martine, Krauter Jürgen, Pabst Thomas, Theobald Matthias, Schlenk Richard F., Delwel Ruud, Döhner Konstanze, Löwenberg Bob, Döhner Hartmut, Clinical, Molecular, and Prognostic Significance of WHO Type inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and Various Other 3q Abnormalities in Acute Myeloid Leukemia, 10.1200/jco.2010.29.2771
  26. Man Tsz-Kwong, Lu Xin-Yan, Jaeweon Kim, Perlaky Laszlo, Harris Charles P, Shah Shishir, Ladanyi Marc, Gorlick Richard, Lau Ching C, Rao Pulivarthi H, Genome-wide array comparative genomic hybridization analysis reveals distinct amplifications in osteosarcoma, 10.1186/1471-2407-4-45
  27. Medves S, Duhoux F P, Ferrant A, Toffalini F, Ameye G, Libouton J-M, Poirel H A, Demoulin J-B, KANK1, a candidate tumor suppressor gene, is fused to PDGFRB in an imatinib-responsive myeloid neoplasm with severe thrombocythemia, 10.1038/leu.2010.13
  28. Mochizuki, Blood, 96, 3209 (2000)
  29. Moir, Blood, 64, 553 (1984)
  30. Morishita K., Parganas E., William C. L., Whittaker M. H., Drabkin H., Oval J., Taetle R., Valentine M. B., Ihle J. N., Activation of EVI1 gene expression in human acute myelogenous leukemias by translocations spanning 300-400 kilobases on chromosome band 3q26., 10.1073/pnas.89.9.3937
  31. Mullighan Charles G., Goorha Salil, Radtke Ina, Miller Christopher B., Coustan-Smith Elaine, Dalton James D., Girtman Kevin, Mathew Susan, Ma Jing, Pounds Stanley B., Su Xiaoping, Pui Ching-Hon, Relling Mary V., Evans William E., Shurtleff Sheila A., Downing James R., Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia, 10.1038/nature05690
  32. Mullighan Charles G., Miller Christopher B., Radtke Ina, Phillips Letha A., Dalton James, Ma Jing, White Deborah, Hughes Timothy P., Le Beau Michelle M., Pui Ching-Hon, Relling Mary V., Shurtleff Sheila A., Downing James R., BCR–ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros, 10.1038/nature06866
  33. Mullighan Charles G., Su Xiaoping, Zhang Jinghui, Radtke Ina, Phillips Letha A.A., Miller Christopher B., Ma Jing, Liu Wei, Cheng Cheng, Schulman Brenda A., Harvey Richard C., Chen I-Ming, Clifford Robert J., Carroll William L., Reaman Gregory, Bowman W. Paul, Devidas Meenakshi, Gerhard Daniela S., Yang Wenjian, Relling Mary V., Shurtleff Sheila A., Campana Dario, Borowitz Michael J., Pui Ching-Hon, Smith Malcolm, Hunger Stephen P., Willman Cheryl L., Downing James R., Deletion ofIKZF1and Prognosis in Acute Lymphoblastic Leukemia, 10.1056/nejmoa0808253
  34. Nishikata I., A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed mainly in t(1;3)(p36;q21)-positive AML and blocks G-CSF-induced myeloid differentiation, 10.1182/blood-2002-12-3944
  35. Nucifora G., Begy C. R., Kobayashi H., Roulston D., Claxton D., Pedersen-Bjergaard J., Parganas E., Ihle J. N., Rowley J. D., Consistent intergenic splicing and production of multiple transcripts between AML1 at 21q22 and unrelated genes at 3q26 in (3;21)(q26;q22) translocations., 10.1073/pnas.91.9.4004
  36. Rippe Volkhard, Drieschner Norbert, Meiboom Maren, Escobar Hugo Murua, Bonk Ulrich, Belge Gazanfer, Bullerdiek Jörn, Identification of a gene rearranged by 2p21 aberrations in thyroid adenomas, 10.1038/sj.onc.1206867
  37. Roche-Lestienne C., Deluche L., Corm S., Tigaud I., Joha S., Philippe N., Geffroy S., Lai J.-L., Nicolini F.-E., Preudhomme C., , RUNX1 DNA-binding mutations and RUNX1-PRDM16 cryptic fusions in BCR-ABL+ leukemias are frequently associated with secondary trisomy 21 and may contribute to clonal evolution and imatinib resistance, 10.1182/blood-2007-07-102533
  38. Sakai Ikuya, Tamura Tatsushiro, Narumi Hirosi, Uchida Naoyuki, Yakushijin Yoshihiro, Hato Takaaki, Fujita Shigeru, Yasukawa Masaki, NovelRUNX1-PRDM16 fusion transcripts in a patient with acute myeloid leukemia showing t(1;21)(p36;q22), 10.1002/gcc.20241
  39. Schneider Robert, Bannister Andrew J., Kouzarides Tony, Unsafe SETs: histone lysine methyltransferases and cancer, 10.1016/s0968-0004(02)02141-2
  40. Seale Patrick, Bjork Bryan, Yang Wenli, Kajimura Shingo, Chin Sherry, Kuang Shihuan, Scimè Anthony, Devarakonda Srikripa, Conroe Heather M., Erdjument-Bromage Hediye, Tempst Paul, Rudnicki Michael A., Beier David R., Spiegelman Bruce M., PRDM16 controls a brown fat/skeletal muscle switch, 10.1038/nature07182
  41. Shimizu Seiichi, Suzukawa Kazumi, Kodera Takao, Nagasawa Toshiro, Abe Tsukasa, Taniwaki Masafumi, Yagasaki Fumiharu, Tanaka Hideo, Fujisawa Shin, Johansson Bertil, Ahlgren Tomas, Yokota Jun, Morishita Kazuhiro, Identification of breakpoint cluster regions at 1p36.3 and 3q21 in hematologic malignancies with t(1;3)(p36;q21), 10.1002/(sici)1098-2264(200003)27:3<229::aid-gcc2>3.0.co;2-0
  42. Shing, Journal of Clinical Investigation, 117, 3696 (2007)
  43. Stevens-Kroef M-J P L, Schoenmakers E F P M, van Kraaij M, Huys E, Vermeulen S, van der Reijden B, van Kessel A Geurts, Identification of truncated RUNX1 and RUNX1-PRDM16 fusion transcripts in a case of t(1;21)(p36;q22)-positive therapy-related AML, 10.1038/sj.leu.2404210
  44. Storlazzi C.T., Albano F., Guastadisegni M.C., Impera L., Mühlematter D., Meyer-Monard S., Wuillemin W., Rocchi M., Jotterand M., Upregulation of MEL1 and FLJ42875 genes by position effect resulting from a t(1;2)(p36;p21) occurring during evolution of chronic myelomonocytic leukemia, 10.1016/j.bcmd.2007.11.004
  45. Swerdlow, WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (2008)
  46. Takahata Mami, Inoue Yasumichi, Tsuda Hitoshi, Imoto Issei, Koinuma Daizo, Hayashi Makoto, Ichikura Takashi, Yamori Takao, Nagasaki Koichi, Yoshida Mika, Matsuoka Masao, Morishita Kazuhiro, Yuki Keiko, Hanyu Aki, Miyazawa Keiji, Inazawa Johji, Miyazono Kohei, Imamura Takeshi, SKI and MEL1 Cooperate to Inhibit Transforming Growth Factor-β Signal in Gastric Cancer Cells, 10.1074/jbc.m808989200
  47. Tefferi A, Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1, 10.1038/leu.2010.69
  48. Warner Dennis R., Horn Kristin H., Mudd Lisa, Webb Cynthia L., Greene Robert M., Pisano M. Michele, PRDM16/MEL1: A novel Smad binding protein expressed in murine embryonic orofacial tissue, 10.1016/j.bbamcr.2007.03.016
  49. Xiao Zhijian, Zhang Meirong, Liu Xuping, Zhang Yue, Yang Lin, Hao Yushu, MEL1S, not MEL1, is overexpressed in myelodysplastic syndromes patients with t(1;3)(p36;q21), 10.1016/j.leukres.2005.07.002
  50. Xinh Phan Thi, Tri Nguyen Khanh, Nagao Hiromasa, Nakazato Hiroshi, Taketazu Fumitoshi, Fujisawa Shin, Yagasaki Fumiharu, Chen Ying Zhang, Hayashi Yasuhide, Toyoda Atsushi, Hattori Masahira, Sakaki Yoshiyuki, Tokunaga Katsushi, Sato Yuko, Breakpoints at 1p36.3 in three MDS/AML(M4) patients with t(1;3)(p36;q21) occur in the first intron and in the 5? region ofMEL1, 10.1002/gcc.10176
  51. Yoshida M., Aberrant expression of the MEL1S gene identified in association with hypomethylation in adult T-cell leukemia cells, 10.1182/blood-2003-07-2482
  52. Zhao Chunxia, Matveeva Elena A., Ren Qiansheng, Whiteheart Sidney W., Dissecting theN-Ethylmaleimide-sensitive Factor : REQUIRED ELEMENTS OF THE N AND D1 DOMAINS, 10.1074/jbc.m109.056739
  53. Duhoux Francois P., Ameye Geneviève, Lambot Virginie, Herens Christian, Lambert Frédéric, Raynaud Sophie, Wlodarska Iwona, Michaux Lucienne, Roche-Lestienne Catherine, Labis Elise, Taviaux Sylvie, Chapiro Elise, Khac Florence Nguyen, Struski Stéphanie, Dobbelstein Sophie, Dastugue Nicole, Lippert Eric, Speleman Frank, Van Roy Nadine, De Weer An, Rack Katrina, Talmant Pascaline, Richebourg Steven, Mugneret Francine, Tigaud Isabelle, Mozziconacci Marie-Joëlle, Laibe Sophy, Nadal Nathalie, Terré Christine, Libouton Jeanne-Marie, Decottignies Anabelle, Vikkula Miikka, Poirel Hélène A., , Refinement of 1p36 Alterations Not Involving PRDM16 in Myeloid and Lymphoid Malignancies, 10.1371/journal.pone.0026311
Bibliographic reference Duhoux, François ; Ameye, Geneviève ; Montano Almendras, Carmen Patricia ; Bahloula, Khadija ; Mozziconacci, Marie-Joëlle ; et. al. PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies. In: British Journal of Haematology, Vol. 156, no. 1, p. 76-88 (2012)
Permanent URL http://hdl.handle.net/2078.1/105465