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2. New insights to the MLL recombinome of acute leukemias

Author

Meyer, C, Kowarz, E, Hofmann, J, Renneville, A, Zuna, J, Trka, J, Ben Abdelali, R, Macintyre, E, De Braekeleer, E, De Braekeleer, M, Delabesse, E, de Oliveira, M P, Cavé, H, Clappier, E, van Dongen, J J M, Balgobind, B V, van den Heuvel-Eibrink, M M, Beverloo, H B, Panzer-Grümayer, R, Teigler-Schlegel, A, Harbott, J, Kjeldsen, E, Schnittger, S, Koehl, U, Gruhn, B, Heidenreich, O, Chan, L C, Yip, S F, Krzywinski, M, Eckert, C, Möricke, A, Schrappe, M, Alonso, C N, Schäfer, B W, Krauter, J, Lee, D A, zur Stadt, U, Te Kronnie, G, Sutton, R, Izraeli, S, Trakhtenbrot, L, Lo Nigro, L, Tsaur, G, Fechina, L, Szczepanski, T, Strehl, S, Ilencikova, D, Molkentin, M, Burmeister, T, Dingermann, T, Klingebiel, T, and Marschalek, R

Published
2009
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3. The MLL recombinome of acute leukemias in 2013

Author

Meyer, C, Hofmann, J, Burmeister, T, Gröger, D, Park, T S, Emerenciano, M, Pombo de Oliveira, M, Renneville, A, Villarese, P, Macintyre, E, Cavé, H, Clappier, E, Mass-Malo, K, Zuna, J, Trka, J, De Braekeleer, E, De Braekeleer, M, Oh, S H, Tsaur, G, Fechina, L, van der Velden, V HJ, van Dongen, J JM, Delabesse, E, Binato, R, Silva, M LM, Kustanovich, A, Aleinikova, O, Harris, M H, Lund-Aho, T, Juvonen, V, Heidenreich, O, Vormoor, J, Choi, W WL, Jarosova, M, Kolenova, A, Bueno, C, Menendez, P, Wehner, S, Eckert, C, Talmant, P, Tondeur, S, Lippert, E, Launay, E, Henry, C, Ballerini, P, Lapillone, H, Callanan, M B, Cayuela, J M, Herbaux, C, Cazzaniga, G, Kakadiya, P M, Bohlander, S, Ahlmann, M, Choi, J R, Gameiro, P, Lee, D S, Krauter, J, Cornillet-Lefebvre, P, Te Kronnie, G, Schäfer, B W, Kubetzko, S, Alonso, C N, zur Stadt, U, Sutton, R, Venn, N C, Izraeli, S, Trakhtenbrot, L, Madsen, H O, Archer, P, Hancock, J, Cerveira, N, Teixeira, M R, Lo Nigro, L, Möricke, A, Stanulla, M, Schrappe, M, Sedék, L, Szczepański, T, Zwaan, C M, Coenen, E A, van den Heuvel-Eibrink, M M, Strehl, S, Dworzak, M, Panzer-Grümayer, R, Dingermann, T, Klingebiel, T, and Marschalek, R

Published
2013
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4. The MLL recombinome of acute leukemias in 2017

Author

Meyer, C., Burmeister, T., Groeger, D., Tsaur, G., Fechina, L., Renneville, A., Sutton, R., Venn, N. C., Emerenciano, M., Pombo-de-Oliveira, M. S., Blunck, C. Barbieri, Lopes, B. Almeida, Zuna, J., Trka, J., Ballerini, P., Lapillonne, H., De Braekeleer, M., Cazzaniga, G., Abascal, L. Corral, van der Velden, V. H. J., Delabesse, E., Park, T. S., Oh, S. H., Silva, M. L. M., Lund-Aho, T., Juvonen, V., Moore, A. S., Heidenreich, O., Vormoor, J., Zerkalenkova, E., Olshanskaya, Y., Bueno, C., Menendez, P., Teigler-Schlegel, A., zur Stadt, U., Lentes, J., Goehring, G., Kustanovich, A., Aleinikova, O., Schafer, B. W., Kubetzko, S., Madsen, H. O., Gruhn, B., Duarte, X., Gameiro, P., Lippert, E., Bidet, A., Cayuela, J. M., Clappier, E., Alonso, C. N., Zwaan, C. M., van den Heuvel-Eibrink, M. M., Izraeli, S., Trakhtenbrot, L., Archer, P., Hancock, J., Moericke, A., Alten, J., Schrappe, M., Stanulla, M., Strehl, S., Attarbaschi, A., Dworzak, M., Haas, O. A., Panzer-Gruemayer, R., Sedek, L., Szczepanski, T., Caye, A., Suarez, L., Cave, H., Marschalek, R., Meyer, C., Burmeister, T., Groeger, D., Tsaur, G., Fechina, L., Renneville, A., Sutton, R., Venn, N. C., Emerenciano, M., Pombo-de-Oliveira, M. S., Blunck, C. Barbieri, Lopes, B. Almeida, Zuna, J., Trka, J., Ballerini, P., Lapillonne, H., De Braekeleer, M., Cazzaniga, G., Abascal, L. Corral, van der Velden, V. H. J., Delabesse, E., Park, T. S., Oh, S. H., Silva, M. L. M., Lund-Aho, T., Juvonen, V., Moore, A. S., Heidenreich, O., Vormoor, J., Zerkalenkova, E., Olshanskaya, Y., Bueno, C., Menendez, P., Teigler-Schlegel, A., zur Stadt, U., Lentes, J., Goehring, G., Kustanovich, A., Aleinikova, O., Schafer, B. W., Kubetzko, S., Madsen, H. O., Gruhn, B., Duarte, X., Gameiro, P., Lippert, E., Bidet, A., Cayuela, J. M., Clappier, E., Alonso, C. N., Zwaan, C. M., van den Heuvel-Eibrink, M. M., Izraeli, S., Trakhtenbrot, L., Archer, P., Hancock, J., Moericke, A., Alten, J., Schrappe, M., Stanulla, M., Strehl, S., Attarbaschi, A., Dworzak, M., Haas, O. A., Panzer-Gruemayer, R., Sedek, L., Szczepanski, T., Caye, A., Suarez, L., Cave, H., and Marschalek, R.

Published
2018

5. The MLL recombinome of acute leukemias in 2017

Author

Meyer, C, Burmeister, T, Gröger, D, Tsaur, G, Fechina, L, Renneville, A, Sutton, R, Venn, N, Emerenciano, M, Pombo-De-Oliveira, M, Barbieri Blunck, C, Almeida Lopes, B, Zuna, J, Trka, J, Ballerini, P, Lapillonne, H, De Braekeleer, M, Cazzaniga, G, Corral Abascal, L, Van Der Velden, V, Delabesse, E, Park, T, Oh, S, Silva, M, Lund-Aho, T, Juvonen, V, Moore, A, Heidenreich, O, Vormoor, J, Zerkalenkova, E, Olshanskaya, Y, Bueno, C, Menendez, P, Teigler-Schlegel, A, Zur Stadt, U, Lentes, J, Göhring, G, Kustanovich, A, Aleinikova, O, Schäfer, B, Kubetzko, S, Madsen, H, Gruhn, B, Duarte, X, Gameiro, P, Lippert, E, Bidet, A, Cayuela, J, Clappier, E, Alonso, C, Zwaan, C, Van Den Heuvel-Eibrink, M, Izraeli, S, Trakhtenbrot, L, Archer, P, Hancock, J, Möricke, A, Alten, J, Schrappe, M, Stanulla, M, Strehl, S, Attarbaschi, A, Dworzak, M, Haas, O, Panzer-Grümayer, R, Sedék, L, Szczepa, T, Caye, A, Suarez, L, Cavé, H, Marschalek, R, Meyer, C., Burmeister, T., Gröger, D., Tsaur, G., Fechina, L., Renneville, A., Sutton, R., Venn, N. C., Emerenciano, M., Pombo-De-Oliveira, M. S., Barbieri Blunck, C., Almeida Lopes, B., Zuna, J., Trka, J., Ballerini, P., Lapillonne, H., De Braekeleer, M., Cazzaniga, G., Corral Abascal, L., Van Der Velden, V. H. J., Delabesse, E., Park, T. S., Oh, S. H., Silva, M. L. M., Lund-Aho, T., Juvonen, V., Moore, A. S., Heidenreich, O., Vormoor, J., Zerkalenkova, E., Olshanskaya, Y., Bueno, C., Menendez, P., Teigler-Schlegel, A., Zur Stadt, U., Lentes, J., Göhring, G., Kustanovich, A., Aleinikova, O., Schäfer, B. W., Kubetzko, S., Madsen, H. O., Gruhn, B., Duarte, X., Gameiro, P., Lippert, E., Bidet, A., Cayuela, J. M., Clappier, E., Alonso, C. N., Zwaan, C. M., Van Den Heuvel-Eibrink, M. M., Izraeli, S., Trakhtenbrot, L., Archer, P., Hancock, J., Möricke, A., Alten, J., Schrappe, M., Stanulla, M., Strehl, S., Attarbaschi, A., Dworzak, M., Haas, O. A., Panzer-Grümayer, R., Sedék, L., Szczepa, T., Caye, A., Suarez, L., Cavé, H., Marschalek, R., Meyer, C, Burmeister, T, Gröger, D, Tsaur, G, Fechina, L, Renneville, A, Sutton, R, Venn, N, Emerenciano, M, Pombo-De-Oliveira, M, Barbieri Blunck, C, Almeida Lopes, B, Zuna, J, Trka, J, Ballerini, P, Lapillonne, H, De Braekeleer, M, Cazzaniga, G, Corral Abascal, L, Van Der Velden, V, Delabesse, E, Park, T, Oh, S, Silva, M, Lund-Aho, T, Juvonen, V, Moore, A, Heidenreich, O, Vormoor, J, Zerkalenkova, E, Olshanskaya, Y, Bueno, C, Menendez, P, Teigler-Schlegel, A, Zur Stadt, U, Lentes, J, Göhring, G, Kustanovich, A, Aleinikova, O, Schäfer, B, Kubetzko, S, Madsen, H, Gruhn, B, Duarte, X, Gameiro, P, Lippert, E, Bidet, A, Cayuela, J, Clappier, E, Alonso, C, Zwaan, C, Van Den Heuvel-Eibrink, M, Izraeli, S, Trakhtenbrot, L, Archer, P, Hancock, J, Möricke, A, Alten, J, Schrappe, M, Stanulla, M, Strehl, S, Attarbaschi, A, Dworzak, M, Haas, O, Panzer-Grümayer, R, Sedék, L, Szczepa, T, Caye, A, Suarez, L, Cavé, H, Marschalek, R, Meyer, C., Burmeister, T., Gröger, D., Tsaur, G., Fechina, L., Renneville, A., Sutton, R., Venn, N. C., Emerenciano, M., Pombo-De-Oliveira, M. S., Barbieri Blunck, C., Almeida Lopes, B., Zuna, J., Trka, J., Ballerini, P., Lapillonne, H., De Braekeleer, M., Cazzaniga, G., Corral Abascal, L., Van Der Velden, V. H. J., Delabesse, E., Park, T. S., Oh, S. H., Silva, M. L. M., Lund-Aho, T., Juvonen, V., Moore, A. S., Heidenreich, O., Vormoor, J., Zerkalenkova, E., Olshanskaya, Y., Bueno, C., Menendez, P., Teigler-Schlegel, A., Zur Stadt, U., Lentes, J., Göhring, G., Kustanovich, A., Aleinikova, O., Schäfer, B. W., Kubetzko, S., Madsen, H. O., Gruhn, B., Duarte, X., Gameiro, P., Lippert, E., Bidet, A., Cayuela, J. M., Clappier, E., Alonso, C. N., Zwaan, C. M., Van Den Heuvel-Eibrink, M. M., Izraeli, S., Trakhtenbrot, L., Archer, P., Hancock, J., Möricke, A., Alten, J., Schrappe, M., Stanulla, M., Strehl, S., Attarbaschi, A., Dworzak, M., Haas, O. A., Panzer-Grümayer, R., Sedék, L., Szczepa, T., Caye, A., Suarez, L., Cavé, H., and Marschalek, R.

Abstract

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients

Published
2018

6. The MLL recombinome of acute leukemias in 2017

Author

Hubrecht Institute with UMC, Meyer, C, Burmeister, T, Gröger, D, Tsaur, G, Fechina, L, Renneville, A, Sutton, R, Venn, N C, Emerenciano, M, Pombo-de-Oliveira, M S, Barbieri Blunck, C, Almeida Lopes, B, Zuna, J, Trka, J, Ballerini, P, Lapillonne, H, De Braekeleer, M, Cazzaniga, G, Corral Abascal, L, van der Velden, V H J, Delabesse, E, Park, T S, Oh, S H, Silva, M L M, Lund-Aho, T, Juvonen, V, Moore, A S, Heidenreich, O, Vormoor, J, Zerkalenkova, E, Olshanskaya, Y, Bueno, C, Menendez, P, Teigler-Schlegel, A, Zur Stadt, U, Lentes, J, Göhring, G, Kustanovich, A, Aleinikova, O, Schäfer, B W, Kubetzko, S, Madsen, H O, Gruhn, B, Duarte, X, Gameiro, P, Lippert, E, Bidet, A, Cayuela, J M, Clappier, E, Alonso, C N, Zwaan, C M, van den Heuvel-Eibrink, M M, Izraeli, S, Trakhtenbrot, L, Archer, P, Hancock, J, Möricke, A, Alten, J, Schrappe, M, Stanulla, M, Strehl, S, Attarbaschi, A, Dworzak, M, Haas, O A, Panzer-Grümayer, R, Sedék, L, Szczepański, T, Caye, A, Suarez, L, Cavé, H, Marschalek, R, Hubrecht Institute with UMC, Meyer, C, Burmeister, T, Gröger, D, Tsaur, G, Fechina, L, Renneville, A, Sutton, R, Venn, N C, Emerenciano, M, Pombo-de-Oliveira, M S, Barbieri Blunck, C, Almeida Lopes, B, Zuna, J, Trka, J, Ballerini, P, Lapillonne, H, De Braekeleer, M, Cazzaniga, G, Corral Abascal, L, van der Velden, V H J, Delabesse, E, Park, T S, Oh, S H, Silva, M L M, Lund-Aho, T, Juvonen, V, Moore, A S, Heidenreich, O, Vormoor, J, Zerkalenkova, E, Olshanskaya, Y, Bueno, C, Menendez, P, Teigler-Schlegel, A, Zur Stadt, U, Lentes, J, Göhring, G, Kustanovich, A, Aleinikova, O, Schäfer, B W, Kubetzko, S, Madsen, H O, Gruhn, B, Duarte, X, Gameiro, P, Lippert, E, Bidet, A, Cayuela, J M, Clappier, E, Alonso, C N, Zwaan, C M, van den Heuvel-Eibrink, M M, Izraeli, S, Trakhtenbrot, L, Archer, P, Hancock, J, Möricke, A, Alten, J, Schrappe, M, Stanulla, M, Strehl, S, Attarbaschi, A, Dworzak, M, Haas, O A, Panzer-Grümayer, R, Sedék, L, Szczepański, T, Caye, A, Suarez, L, Cavé, H, and Marschalek, R

Published
2018

7. The MLL recombinome of acute leukemias in 2017

Author

Meyer, C, primary, Burmeister, T, additional, Gröger, D, additional, Tsaur, G, additional, Fechina, L, additional, Renneville, A, additional, Sutton, R, additional, Venn, N C, additional, Emerenciano, M, additional, Pombo-de-Oliveira, M S, additional, Barbieri Blunck, C, additional, Almeida Lopes, B, additional, Zuna, J, additional, Trka, J, additional, Ballerini, P, additional, Lapillonne, H, additional, De Braekeleer, M, additional, Cazzaniga, G, additional, Corral Abascal, L, additional, van der Velden, V H J, additional, Delabesse, E, additional, Park, T S, additional, Oh, S H, additional, Silva, M L M, additional, Lund-Aho, T, additional, Juvonen, V, additional, Moore, A S, additional, Heidenreich, O, additional, Vormoor, J, additional, Zerkalenkova, E, additional, Olshanskaya, Y, additional, Bueno, C, additional, Menendez, P, additional, Teigler-Schlegel, A, additional, zur Stadt, U, additional, Lentes, J, additional, Göhring, G, additional, Kustanovich, A, additional, Aleinikova, O, additional, Schäfer, B W, additional, Kubetzko, S, additional, Madsen, H O, additional, Gruhn, B, additional, Duarte, X, additional, Gameiro, P, additional, Lippert, E, additional, Bidet, A, additional, Cayuela, J M, additional, Clappier, E, additional, Alonso, C N, additional, Zwaan, C M, additional, van den Heuvel-Eibrink, M M, additional, Izraeli, S, additional, Trakhtenbrot, L, additional, Archer, P, additional, Hancock, J, additional, Möricke, A, additional, Alten, J, additional, Schrappe, M, additional, Stanulla, M, additional, Strehl, S, additional, Attarbaschi, A, additional, Dworzak, M, additional, Haas, O A, additional, Panzer-Grümayer, R, additional, Sedék, L, additional, Szczepański, T, additional, Caye, A, additional, Suarez, L, additional, Cavé, H, additional, and Marschalek, R, additional

Published
2017
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8. The MLL recombinome of acute leukemias in 2017.

Author

Meyer C, Burmeister T, Gröger D, Tsaur G, Fechina L, Renneville A, Sutton R, Venn NC, Emerenciano M, Pombo-de-Oliveira MS, Barbieri Blunck C, Almeida Lopes B, Zuna J, Trka J, Ballerini P, Lapillonne H, De Braekeleer M, Cazzaniga G, Corral Abascal L, van der Velden VHJ, Delabesse E, Park TS, Oh SH, Silva MLM, Lund-Aho T, Juvonen V, Moore AS, Heidenreich O, Vormoor J, Zerkalenkova E, Olshanskaya Y, Bueno C, Menendez P, Teigler-Schlegel A, Zur Stadt U, Lentes J, Göhring G, Kustanovich A, Aleinikova O, Schäfer BW, Kubetzko S, Madsen HO, Gruhn B, Duarte X, Gameiro P, Lippert E, Bidet A, Cayuela JM, Clappier E, Alonso CN, Zwaan CM, van den Heuvel-Eibrink MM, Izraeli S, Trakhtenbrot L, Archer P, Hancock J, Möricke A, Alten J, Schrappe M, Stanulla M, Strehl S, Attarbaschi A, Dworzak M, Haas OA, Panzer-Grümayer R, Sedék L, Szczepański T, Caye A, Suarez L, Cavé H, and Marschalek R

Subjects
Adult, Child, Chromosome Aberrations, Chromosome Breakage, Female, Gene Rearrangement genetics, Humans, Infant, Male, Oncogene Proteins, Fusion genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Translocation, Genetic genetics, Histone-Lysine N-Methyltransferase genetics, Leukemia, Myeloid, Acute genetics, Myeloid-Lymphoid Leukemia Protein genetics
Abstract

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.

Published
2018
Full Text
View/download PDF

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