Genes encoding members of the JAK-STAT pathway or epigenetic regulators are recurrently mutated in T-cell prolymphocytic leukaemia
Cristina López
Institute for Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig Holstein, Kiel, Germany
Contributed equally.Search for more papers by this authorCorresponding Author
Anke K. Bergmann
Institute for Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig Holstein, Kiel, Germany
Department of Paediatrics, Christian-Albrechts-University Kiel & University Hospital Schleswig Holstein, Kiel, Germany
Contributed equally.Correspondence: Dr. Anke K. Bergmann, Institute for Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 24, 24105 Kiel, Germany.
E-mail: [email protected]
Search for more papers by this authorUlrike Paul
Institute for Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig Holstein, Kiel, Germany
Search for more papers by this authorEva M. Murga Penas
Institute for Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig Holstein, Kiel, Germany
Search for more papers by this authorInga Nagel
Institute for Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig Holstein, Kiel, Germany
Search for more papers by this authorMatthew J. Betts
Cell Networks, Bioquant, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorPatricia Johansson
Department of Haematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Faculty of Medicine, Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen, Germany
Search for more papers by this authorMatthias Ritgen
Second Department of Medicine, University Hospital of Schleswig-Holstein, Kiel, Germany
Search for more papers by this authorTycho Baumann
Department of Haematology, Hospital Clínic, Institut d′Investigaciones Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain
Search for more papers by this authorMarta Aymerich
Haematopathology Unit, Hospital Clínic, Institut d′Investigaciones Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
Search for more papers by this authorSandrine Jayne
Ernest and Helen Scott Haematological Research Institute, University of Leicester, Leicester, UK
Search for more papers by this authorRobert B. Russell
Cell Networks, Bioquant, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorElias Campo
Haematopathology Unit, Hospital Clínic, Institut d′Investigaciones Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
Search for more papers by this authorMartin JS Dyer
Ernest and Helen Scott Haematological Research Institute, University of Leicester, Leicester, UK
Search for more papers by this authorJan Dürig
Department of Haematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
German Cancer Consortium (DKTK), Heidelberg, Germany
Search for more papers by this authorReiner Siebert
Institute for Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig Holstein, Kiel, Germany
Search for more papers by this authorCristina López
Institute for Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig Holstein, Kiel, Germany
Contributed equally.Search for more papers by this authorCorresponding Author
Anke K. Bergmann
Institute for Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig Holstein, Kiel, Germany
Department of Paediatrics, Christian-Albrechts-University Kiel & University Hospital Schleswig Holstein, Kiel, Germany
Contributed equally.Correspondence: Dr. Anke K. Bergmann, Institute for Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 24, 24105 Kiel, Germany.
E-mail: [email protected]
Search for more papers by this authorUlrike Paul
Institute for Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig Holstein, Kiel, Germany
Search for more papers by this authorEva M. Murga Penas
Institute for Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig Holstein, Kiel, Germany
Search for more papers by this authorInga Nagel
Institute for Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig Holstein, Kiel, Germany
Search for more papers by this authorMatthew J. Betts
Cell Networks, Bioquant, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorPatricia Johansson
Department of Haematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Faculty of Medicine, Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen, Germany
Search for more papers by this authorMatthias Ritgen
Second Department of Medicine, University Hospital of Schleswig-Holstein, Kiel, Germany
Search for more papers by this authorTycho Baumann
Department of Haematology, Hospital Clínic, Institut d′Investigaciones Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain
Search for more papers by this authorMarta Aymerich
Haematopathology Unit, Hospital Clínic, Institut d′Investigaciones Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
Search for more papers by this authorSandrine Jayne
Ernest and Helen Scott Haematological Research Institute, University of Leicester, Leicester, UK
Search for more papers by this authorRobert B. Russell
Cell Networks, Bioquant, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorElias Campo
Haematopathology Unit, Hospital Clínic, Institut d′Investigaciones Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
Search for more papers by this authorMartin JS Dyer
Ernest and Helen Scott Haematological Research Institute, University of Leicester, Leicester, UK
Search for more papers by this authorJan Dürig
Department of Haematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
German Cancer Consortium (DKTK), Heidelberg, Germany
Search for more papers by this authorReiner Siebert
Institute for Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig Holstein, Kiel, Germany
Search for more papers by this authorSummary
T-cell prolymphocytic leukaemia (T-PLL) is an aggressive leukaemia. The primary genetic alteration in T-PLL are the inv(14)(q11q32)/t(14;14)(q11;q32) leading to TRD/TRA-TCL1A fusion, or the t(X;14)(q28;q11) associated with TRD/TRA-MTCP1 fusion. However, additional cooperating abnormalities are necessary for emergence of the full neoplastic phenotype. Though the pattern of secondary chromosomal aberrations is remarkably conserved, targets of the changes are largely unknown. We analysed a cohort of 43 well-characterized T-PLL for hotspot mutations in the genes JAK3, STAT5B and RHOA. Additionally, we selected a subset of 23 T-PLL cases for mutational screening of 54 genes known to be recurrently mutated in T-cell and other haematological neoplasms. Activating mutations in the investigated regions of the JAK3 and STAT5B genes were detected in 30% (13/43) and 21% (8/39) of the cases, respectively, and were mutually exclusive. Further, we identified mutations in the genes encoding the epigenetic regulators EZH2 in 13% (3/23), TET2 in 17% (4/23) and BCOR in 9% (2/23) of the cases. We confirmed that the JAK-STAT pathway is a major mutational target, and identified epigenetic regulators recurrently mutated in T-PLL. These findings complement the mutational spectrum of secondary aberrations in T-PLL and underscore the potential therapeutical relevance of epigenetic regulators in T-PLL.
Supporting Information
| Filename | Description |
|---|---|
| bjh13952-sup-0001-SupInfo.docxWord document, 73.2 KB | Fig S1. FISH results of EZH2 gene. FISH results of case ID 10 showing one green signal for RP11-28C14 clone and two aqua signals for CEP7 probe. Table SI. Characteristics of T-PLL cohort under study. Table SII. Clinical characteristics of 19 T-PLL patients with available clinical data Table SIII. Primers and conditions Table SIV. Gene regions assessed by the TruSight Myeloid Sequencing Panel. Table SV. Basic characteristics of the groups. Table SVI. Mutations detected by hot spot Sanger sequencing and the TruSight Sequencing Panel. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- Adzhubei, I., Jordan, D.M. & Sunyaev, S.R. (2013) Predicting functional effect of human missense mutations using PolyPhen-2. Current Protocols in Human Genetics. Chapter 7, 20. doi: 10.1002/0471142905.hg0720s76
- Bains, T., Heinrich, M.C., Loriaux, M.M., Beadling, C., Nelson, D., Warrick, A., Neff, T.L., Tyner, J.W., Dunlap, J., Corless, C.L. & Fan, G. (2012) Newly described activating JAK3 mutations in T-cell acute lymphoblastic leukemia. Leukemia, 26, 2144–2146.
- Bandapalli, O.R., Schuessele, S., Kunz, J.B., Rausch, T., Stutz, A.M., Tal, N., Geron, I., Gershman, N., Izraeli, S., Eilers, J., Vaezipour, N., Kirschner-Schwabe, R., Hof, J., von Stackelberg, A., Schrappe, M., Stanulla, M., Zimmermann, M., Koehler, R., Avigad, S., Handgretinger, R., Frismantas, V., Bourquin, J.P., Bornhauser, B., Korbel, J.O., Muckenthaler, M.U. & Kulozik, A.E. (2014) The activating STAT5B N642H mutation is a common abnormality in pediatric T-cell acute lymphoblastic leukemia and confers a higher risk of relapse. Haematologica, 99, e188–e192.
- Bellanger, D., Jacquemin, V., Chopin, M., Pierron, G., Bernard, O.A., Ghysdael, J. & Stern, M.H. (2014) Recurrent JAK1 and JAK3 somatic mutations in T-cell prolymphocytic leukemia. Leukemia, 28, 417–419.
- Bergmann, A.K., Schneppenheim, S., Seifert, M., Betts, M.J., Haake, A., Lopez, C., Maria Murga Penas, E., Vater, I., Jayne, S., Dyer, M.J., Schrappe, M., Dührsen, U., Ammerpohl, O., Russell, R.B., Kuppers, R., Dürig, J. & Siebert, R. (2014) Recurrent mutation of JAK3 in T-cell prolymphocytic leukemia. Genes Chromosomes Cancer, 53, 309–316.
- Beroud, C., Collod-Beroud, G., Boileau, C., Soussi, T. & Junien, C. (2000) UMD (Universal mutation database): a generic software to build and analyze locus-specific databases. Human Mutation, 15, 86–94.
10.1002/(SICI)1098-1004(200001)15:1<86::AID-HUMU16>3.0.CO;2-4 CAS PubMed Web of Science® Google Scholar
- Bertos, N.R., Wang, A.H. & Yang, X.J. (2001) Class II histone deacetylases: structure, function, and regulation. Biochemistry and Cell Biology, 79, 243–252.
- Betts, M.J., Lu, Q., Jiang, Y., Drusko, A., Wichmann, O., Utz, M., Valtierra-Gutierrez, I.A., Schlesner, M., Jaeger, N., Jones, D.T., Pfister, S., Lichter, P., Eils, R., Siebert, R., Bork, P., Apic, G., Gavin, A.C. & Russell, R.B. (2015) Mechismo: predicting the mechanistic impact of mutations and modifications on molecular interactions. Nucleic Acids Research, 43, e10.
- Bilori, B., Thota, S., Clemente, M.J., Patel, B., Jerez, A., Afable, M. & Maciejewski, J.P. (2015) Tofacitinib as a novel salvage therapy for refractory T cell large granular lymphocytic leukemia. Leukemia, 29, 2427–2429.
- Bouchekioua, A., Scourzic, L., de Wever, O., Zhang, Y., Cervera, P., Aline-Fardin, A., Mercher, T., Gaulard, P., Nyga, R., Jeziorowska, D., Douay, L., Vainchenker, W., Louache, F., Gespach, C., Solary, E. & Coppo, P. (2014) JAK3 deregulation by activating mutations confers invasive growth advantage in extranodal nasal-type natural killer cell lymphoma. Leukemia, 28, 338–348.
- Cornejo, M.G., Kharas, M.G., Werneck, M.B., Le Bras, S., Moore, S.A., Ball, B., Beylot-Barry, M., Rodig, S.J., Aster, J.C., Lee, B.H., Cantor, H., Merlio, J.P., Gilliland, D.G. & Mercher, T. (2009) Constitutive JAK3 activation induces lymphoproliferative syndromes in murine bone marrow transplantation models. Blood, 113, 2746–2754.
- Damm, F., Chesnais, V., Nagata, Y., Yoshida, K., Scourzic, L., Okuno, Y., Itzykson, R., Sanada, M., Shiraishi, Y., Gelsi-Boyer, V., Renneville, A., Miyano, S., Mori, H., Shih, L.Y., Park, S., Dreyfus, F., Guerci-Bresler, A., Solary, E., Rose, C., Cheze, S., Prebet, T., Vey, N., Legentil, M., Duffourd, Y., de Botton, S., Preudhomme, C., Birnbaum, D., Bernard, O.A., Ogawa, S., Fontenay, M. & Kosmider, O. (2013) BCOR and BCORL1 mutations in myelodysplastic syndromes and related disorders. Blood, 122, 3169–3177.
- Dürig, J., Bug, S., Klein-Hitpass, L., Boes, T., Jons, T., Martin-Subero, J.I., Harder, L., Baudis, M., Dührsen, U. & Siebert, R. (2007) Combined single nucleotide polymorphism-based genomic mapping and global gene expression profiling identifies novel chromosomal imbalances, mechanisms and candidate genes important in the pathogenesis of T-cell prolymphocytic leukemia with inv(14)(q11q32). Leukemia, 21, 2153–2163.
- Elliott, N.E., Cleveland, S.M., Grann, V., Janik, J., Waldmann, T.A. & Dave, U.P. (2011) FERM domain mutations induce gain of function in JAK3 in adult T-cell leukemia/lymphoma. Blood, 118, 3911–3921.
- Ernst, T., Chase, A.J., Score, J., Hidalgo-Curtis, C.E., Bryant, C., Jones, A.V., Waghorn, K., Zoi, K., Ross, F.M., Reiter, A., Hochhaus, A., Drexler, H.G., Duncombe, A., Cervantes, F., Oscier, D., Boultwood, J., Grand, F.H. & Cross, N.C. (2010) Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nature Genetics, 42, 722–726.
- Fisch, P., Forster, A., Sherrington, P.D., Dyer, M.J. & Rabbitts, T.H. (1993) The chromosomal translocation t(X;14)(q28;q11) in T-cell pro-lymphocytic leukaemia breaks within one gene and activates another. Oncogene, 8, 3271–3276.
- Gesk, S., Martin-Subero, J.I., Harder, L., Luhmann, B., Schlegelberger, B., Calasanz, M.J., Grote, W. & Siebert, R. (2003) Molecular cytogenetic detection of chromosomal breakpoints in T-cell receptor gene loci. Leukemia, 17, 738–745.
- Herling, M., Patel, K.A., Teitell, M.A., Konopleva, M., Ravandi, F., Kobayashi, R. & Jones, D. (2008) High TCL1 expression and intact T-cell receptor signaling define a hyperproliferative subset of T-cell prolymphocytic leukemia. Blood, 111, 328–337.
- Hu, L., Li, Z., Cheng, J., Rao, Q., Gong, W., Liu, M., Shi, Y.G., Zhu, J., Wang, P. & Xu, Y. (2013) Crystal structure of TET2-DNA complex: insight into TET-mediated 5mC oxidation. Cell, 155, 1545–1555.
- Kiel, M.J., Velusamy, T., Rolland, D., Sahasrabuddhe, A.A., Chung, F., Bailey, N.G., Schrader, A., Li, B., Li, J.Z., Ozel, A.B., Betz, B.L., Miranda, R.N., Medeiros, L.J., Zhao, L., Herling, M., Lim, M.S. & Elenitoba-Johnson, K.S. (2014) Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia. Blood, 124, 1460–1472.
- Ko, M., Huang, Y., Jankowska, A.M., Pape, U.J., Tahiliani, M., Bandukwala, H.S., An, J., Lamperti, E.D., Koh, K.P., Ganetzky, R., Liu, X.S., Aravind, L., Agarwal, S., Maciejewski, J.P. & Rao, A. (2010) Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature, 468, 839–843.
- Konstandin, N., Bultmann, S., Szwagierczak, A., Dufour, A., Ksienzyk, B., Schneider, F., Herold, T., Mulaw, M., Kakadia, P.M., Schneider, S., Spiekermann, K., Leonhardt, H. & Bohlander, S.K. (2011) Genomic 5-hydroxymethylcytosine levels correlate with TET2 mutations and a distinct global gene expression pattern in secondary acute myeloid leukemia. Leukemia, 25, 1649–1652.
- Kontro, M., Kuusanmaki, H., Eldfors, S., Burmeister, T., Andersson, E.I., Bruserud, O., Brummendorf, T.H., Edgren, H., Gjertsen, B.T., Itala-Remes, M., Lagstrom, S., Lohi, O., Lundan, T., Marti, J.M., Majumder, M.M., Parsons, A., Pemovska, T., Rajala, H., Vettenranta, K., Kallioniemi, O., Mustjoki, S., Porkka, K. & Heckman, C.A. (2014) Novel activating STAT5B mutations as putative drivers of T-cell acute lymphoblastic leukemia. Leukemia, 28, 1738–1742.
- Koo, G.C., Tan, S.Y., Tang, T., Poon, S.L., Allen, G.E., Tan, L., Chong, S.C., Ong, W.S., Tay, K., Tao, M., Quek, R., Loong, S., Yeoh, K.W., Yap, S.P., Lee, K.A., Lim, L.C., Tan, D., Goh, C., Cutcutache, I., Yu, W., Ng, C.C., Rajasegaran, V., Heng, H.L., Gan, A., Ong, C.K., Rozen, S., Tan, P., Teh, B.T. & Lim, S.T. (2012) Janus kinase 3-activating mutations identified in natural killer/T-cell lymphoma. Cancer Discovery, 2, 591–597.
- Kumar, P., Henikoff, S. & Ng, P.C. (2009) Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nature Protocols, 4, 1073–1081.
- Le Toriellec, E., Despouy, G., Pierron, G., Gaye, N., Joiner, M., Bellanger, D., Vincent-Salomon, A. & Stern, M.H. (2008) Haploinsufficiency of CDKN1B contributes to leukemogenesis in T-cell prolymphocytic leukemia. Blood, 111, 2321–2328.
- Lemonnier, F., Couronne, L., Parrens, M., Jais, J.P., Travert, M., Lamant, L., Tournillac, O., Rousset, T., Fabiani, B., Cairns, R.A., Mak, T., Bastard, C., Bernard, O.A., de Leval, L. & Gaulard, P. (2012) Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters. Blood, 120, 1466–1469.
- Madani, A., Choukroun, V., Soulier, J., Cacheux, V., Claisse, J.F., Valensi, F., Daliphard, S., Cazin, B., Levy, V., Leblond, V., Daniel, M.T., Sigaux, F. & Stern, M.H. (1996) Expression of p13MTCP1 is restricted to mature T-cell proliferations with t(X;14) translocations. Blood, 87, 1923–1927.
- Matutes, E., Brito-Babapulle, V., Swansbury, J., Ellis, J., Morilla, R., Dearden, C., Sempere, A. & Catovsky, D. (1991) Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia. Blood, 78, 3269–3274.
- Mochizuki-Kashio, M., Aoyama, K., Sashida, G., Oshima, M., Tomioka, T., Muto, T., Wang, C. & Iwama, A. (2015) Ezh2 loss in hematopoietic stem cells predisposes mice to develop heterogeneous malignancies in an Ezh1-depenedent manner. Blood, 126, 1172–1183.
- Morin, R.D., Johnson, N.A., Severson, T.M., Mungall, A.J., An, J., Goya, R., Paul, J.E., Boyle, M., Woolcock, B.W., Kuchenbauer, F., Yap, D., Humphries, R.K., Griffith, O.L., Shah, S., Zhu, H., Kimbara, M., Shashkin, P., Charlot, J.F., Tcherpakov, M., Corbett, R., Tam, A., Varhol, R., Smailus, D., Moksa, M., Zhao, Y., Dlaney, A., Qian, H., Birol, I., Schein, J., Moore, R., Holt, R., Horsman, D.E., Connors, Jm, Jones, S., Aparicio, S., Hirst, M., Gascoyne, R.D. & Marra, M.A. (2010) Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymohomas of germinal-center origin. Nature Genetics, 42, 181–185.
- Narducci, M.G., Virgilio, L., Isobe, M., Stoppacciaro, A., Elli, R., Fiorilli, M., Carbonari, M., Antonelli, A., Chessa, L., Croce, C.M. & Russo, G. (1995) TCL1 oncogene activation in preleukemic T cells from a case of ataxia-telangiectasia. Blood, 86, 2358–2364.
- Nicolae, A., Xi, L., Pittaluga, S., Abdullaev, Z., Pack, S.D., Chen, J., Waldmann, T.A., Jaffe, E.S. & Raffeld, M. (2014) Frequent STAT5B mutations in gammadelta hepatosplenic T-cell lymphomas. Leukemia, 28, 2244–2248.
- Ntziachristos, P., Tsirigos, A., Van Vlierberghe, P., Nedjic, J., Trimarchi, T., Flaherty, M.S., Ferres-Marco, D., da Ros, V., Tang, Z., Siegle, J., Asp, P., Hadler, M., Rigo, I., De Keersmaecker, K., Patel, J., Huynh, T., Utro, F., Poglio, S., Samon, J.B., Paietta, E., Racevskis, J., Rowe, J.M., Rabadan, R., Levine, R.L., Brown, S., Pflumio, F., Dominguez, M., Ferrando, A. & Aifantis, I. (2012) Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia. Nature Medicine, 18, 298–301.
- Oki, Y., Fanale, M., Romaguera, J., Fayad, L., Fowler, N., Copeland, A., Samaniego, F., Kwak, L.W., Neelapu, S., Wang, M., Feng, L. & Younes, A. (2015) Phase II study of an AKT inhibitor MK2206 in patients with relapsed or refractory lymphoma. British Journal of Haematology, 171, 463–470.
- de Oliveira, F.M., Tone, L.G., Simoes, B.P., Rego, E.M., Marinato, A.F., Jacomo, R.H. & Falcao, R.P. (2009) Translocations t(X;14)(q28;q11) and t(Y;14)(q12;q11) in T-cell prolymphocytic leukemia. International Journal of Laboratory Hematology, 31, 453–456.
- Palomero, T., Couronne, L., Khiabanian, H., Kim, M.Y., Ambesi-Impiombato, A., Perez-Garcia, A., Carpenter, Z., Abate, F., Allegretta, M., Haydu, J.E., Jiang, X., Lossos, I.S., Nicolas, C., Balbin, M., Bastard, C., Bhagat, G., Piris, M.A., Campo, E., Bernard, O.A., Rabadan, R. & Ferrando, A.A. (2014) Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nature Genetics, 46, 166–170.
- Pekarsky, Y., Hallas, C., Palamarchuk, A., Koval, A., Bullrich, F., Hirata, Y., Bichi, R., Letofsky, J. & Croce, C.M. (2001) Akt phosphorylates and regulates the orphan nuclear receptor Nur77. Proceedings of the National Academy of Sciences, 98, 3690–3694.
- Puente, X.S., Beà, S., Valdés-Mas, R., Villamor, N., Gutiérrez-Abril, J., Martín-Subero, J.I., Munar, M., Rubio-Pérez, C., Jares, P., Aymerich, M., Baumann, T., Beekman, R., Belver, L., Carrio, A., Castellano, G., Clot, G., Colado, E., Colomer, D., Costa, D., Delgado, J., Enjuanes, A., Estivill, X., Ferrando, A.A., Gelpí, J.L., González, B., González, S., González, M., Gut, M., Hernández-Rivas, J.M., López-Guerra, M., Martín-García, D., Navarro, A., Nicolás, P., Orozco, M., Payer, Á.R., Pinyol, M., Pisano, D.G., Puente, D.A., Queirós, A.C., Quesada, V., Romeo-Casabona, C.M., Royo, C., Rozman, M., Russiñol, N., Salaverría, I., Stamatopoulos, K., Stunnenberg, H.G., Tamborero, D., Terol, M.J., Valencia, A., López-Bigas, N., Torrents, D., Gut, I., López-Guillermo, A., López-Otín, C. & Campo, E. (2015) Non-coding recurrent mutations in chronic lymphocytic leukaemia. Nature, 526, 519–524.
- Rajala, H.L., Eldfors, S., Kuusanmaki, H., van Adrichem, A.J., Olson, T., Lagstrom, S., Andersson, E.I., Jerez, A., Clemente, M.J., Yan, Y., Zhang, D., Awwad, A., Ellonen, P., Kallioniemi, O., Wennerberg, K., Porkka, K., Maciejewski, J.P., Loughran, T.P. Jr, Heckman, C. & Mustjoki, S. (2013) Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia. Blood, 121, 4541–4550.
- Rawlings, J.S., Rosler, K.M. & Harrison, D.A. (2004) The JAK/STAT signaling pathway. Journal of Cell Science, 117, 1281–1283.
- Roy, D.M., Walsh, L.A. & Chan, T.A. (2014) Driver mutations of cancer epigenomes. Protein Cell, 5, 265–296.
- Sakata-Yanagimoto, M., Enami, T., Yoshida, K., Shiraishi, Y., Ishii, R., Miyake, Y., Muto, H., Tsuyama, N., Sato-Otsubo, A., Okuno, Y., Sakata, S., Kamada, Y., Nakamoto-Matsubara, R., Tran, N.B., Izutsu, K., Sato, Y., Ohta, Y., Furuta, J., Shimizu, S., Komeno, T., Ito, T., Noguchi, M., Noguchi, E., Sanada, M., Chiba, K., Tanaka, H., Suzukawa, K., Nanmoku, T., Hasegawa, Y., Nureki, O., Miyano, S., Nakamura, N., Takeuchi, K., Ogawa, S. & Chiba, S. (2014) Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nature Genetics, 46, 171–175.
- Schlegelberger, B., Metzke, S., Harder, S., Zühlke-Jenisch, R., Zhang, Y. & Siebert, R. (1999) Classical and molecular cytogenetics of tumor cells. In: Diagnostic Cytogenetics (ed. by R. Wegener), pp. 151. Springer-Verlag, New York.
10.1007/978-3-642-59918-7_9 Google Scholar
- Shaffer, L.G., McGowan-Jordan, J. & Schmid, M. (2013) ISCN- An International System for Human Cytogenetic Nomenclature. S Karger, Basel.
- Shuai, K. & Liu, B. (2003) Regulation of JAK-STAT signalling in the immune system. Nature Reviews Immunology, 3, 900–911.
- Simon, C., Chagraoui, J., Krosl, J., Gendron, P., Wilhelm, B., Lemieux, S., Boucher, G., Chagnon, P., Drouin, S., Lambert, R., Rondeau, C., Bilodeau, A., Lavallee, S., Sauvageau, M., Hebert, J. & Sauvageau, G. (2012) A key role for EZH2 and associated genes in mouse and human adult T-cell acute leukemia. Genes & Development, 26, 651–656.
- Stankovic, T., Taylor, A.M., Yuille, M.R. & Vorechovsky, I. (2001) Recurrent ATM mutations in T-PLL on diverse haplotypes: no support for their germline origin. Blood, 97, 1517–1518.
- Stengel, A., Kern, W., Zenger, M., Perglerová, K., Schnittger, S., Haferlach, T. & Haferlach, C. (2016) Genetic characterization of T-PLL reveals two major biologic subgroups and JAK3 mutations as prognostic marker. Genes Chromosomes Cancer, 55, 82–94.
- Stern, M.H., Soulier, J., Rosenzwajg, M., Nakahara, K., Canki-Klain, N., Aurias, A., Sigaux, F. & Kirsch, I.R. (1993) MTCP-1: a novel gene on the human chromosome Xq28 translocated to the T cell receptor alpha/delta locus in mature T cell proliferations. Oncogene, 8, 2475–2483.
- Stilgenbauer, S., Schaffner, C., Litterst, A., Liebisch, P., Gilad, S., Bar-Shira, A., James, M.R., Lichter, P. & Dohner, H. (1997) Biallelic mutations in the ATM gene in T-prolymphocytic leukemia. Nature Medicine, 3, 1155–1159.
- Swerdlow, S.H., Campo, E., Harris, N.L., Jaffe, E.S., Pileri, S.A., Stein, H., Thiele, J. & Vardiman, J.W. (eds.) (2008) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC, Lyon.
- Ventura, R.A., Martin-Subero, J.I., Jones, M., McParland, J., Gesk, S., Mason, D.Y. & Siebert, R. (2006) FISH analysis for the detection of lymphoma-associated chromosomal abnormalities in routine paraffin-embedded tissue. The Journal of Molecular Diagnostics : JMD, 8, 141–151.
- Virgilio, L., Lazzeri, C., Bichi, R., Nibu, K., Narducci, M.G., Russo, G., Rothstein, J.L. & Croce, C.M. (1998) Deregulated expression of TCL1 causes T cell leukemia in mice. Proceedings of the National Academy of Sciences of the United States of America, 95, 3885–3889.
- Walters, D.K., Mercher, T., Gu, T.L., O'Hare, T., Tyner, J.W., Loriaux, M., Goss, V.L., Lee, K.A., Eide, C.A., Wong, M.J., Stoffregen, E.P., McGreevey, L., Nardone, J., Moore, S.A., Crispino, J., Boggon, T.J., Heinrich, M.C., Deininger, M.W., Polakiewicz, R.D., Gilliland, D.G. & Druker, B.J. (2006) Activating alleles of JAK3 in acute megakaryoblastic leukemia. Cancer Cell, 10, 65–75.
- Yamashita, Y., Yuan, J., Suetake, I., Suzuki, H., Ishikawa, Y., Choi, Y.L., Ueno, T., Soda, M., Hamada, T., Haruta, H., Takada, S., Miyazaki, Y., Kiyoi, H., Ito, E., Naoe, T., Tomonaga, M., Toyota, M., Tajima, S., Iwama, A. & Mano, H. (2010) Array-based genomic resequencing of human leukemia. Oncogene, 29, 3723–3731.
- Zhang, J., Ding, L., Holmfeldt, L., Wu, G., Heatley, S.L., Payne-Turner, D., Easton, J., Chen, X., Wang, J., Rusch, M., Lu, C., Chen, S.C., Wei, L., Collins-Underwood, J.R., Ma, J., Roberts, K.G., Pounds, S.B., Ulyanov, A., Becksfort, J., Gupta, P., Huether, R., Kriwacki, R.W., Parker, M., McGoldrick, D.J., Zhao, D., Alford, D., Espy, S., Bobba, K.C., Song, G., Pei, D., Cheng, C., Roberts, S., Barbato, M.I., Campana, D., Coustan-Smith, E., Shurtleff, S.A., Raimondi, S.C., Kleppe, M., Cools, J., Shimano, K.A., Hermiston, M.L., Doulatov, S., Eppert, K., Laurenti, E., Notta, F., Dick, J.E., Basso, G., Hunger, S.P., Loh, M.L., Devidas, M., Wood, B., Winter, S., Dunsmore, K.P., Fulton, R.S., Fulton, L.L., Hong, X., Harris, C.C., Dooling, D.J., Ochoa, K., Johnson, K.J., Obenauer, J.C., Evans, W.E., Pui, C.H., Naeve, C.W., Ley, T.J., Mardis, E.R., Wilson, R.K., Downing, J.R. & Mullighan, C.G. (2012) The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature, 481, 157–163.
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