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4 results on '"Lund-Aho, T"'

1. The KMT2A recombinome of acute leukemias in 2023

Author

Meyer, C, Larghero, P, Almeida Lopes, B; https://orcid.org/0000-0003-1072-470X, Burmeister, T; https://orcid.org/0000-0003-4843-2876, Gröger, D, Sutton, R; https://orcid.org/0000-0002-0188-6005, Venn, N C, Cazzaniga, G, Corral Abascal, L, Tsaur, G, Fechina, L, Emerenciano, M; https://orcid.org/0000-0003-2337-8420, Pombo-de-Oliveira, M S; https://orcid.org/0000-0002-1507-004X, Lund-Aho, T, Lundán, T, Montonen, M, Juvonen, V, Zuna, J; https://orcid.org/0000-0002-0887-3709, Trka, J, Ballerini, P, Lapillonne, H, Van der Velden, V H J; https://orcid.org/0000-0001-9457-3763, Sonneveld, E, Delabesse, E, de Matos, R R C; https://orcid.org/0000-0002-8737-1669, Silva, M L M; https://orcid.org/0000-0003-2549-1320, Bomken, S; https://orcid.org/0000-0001-9163-5738, Katsibardi, K, Keernik, M, Schäfer, Beat W; https://orcid.org/0000-0001-5988-2915, et al, Meyer, C, Larghero, P, Almeida Lopes, B; https://orcid.org/0000-0003-1072-470X, Burmeister, T; https://orcid.org/0000-0003-4843-2876, Gröger, D, Sutton, R; https://orcid.org/0000-0002-0188-6005, Venn, N C, Cazzaniga, G, Corral Abascal, L, Tsaur, G, Fechina, L, Emerenciano, M; https://orcid.org/0000-0003-2337-8420, Pombo-de-Oliveira, M S; https://orcid.org/0000-0002-1507-004X, Lund-Aho, T, Lundán, T, Montonen, M, Juvonen, V, Zuna, J; https://orcid.org/0000-0002-0887-3709, Trka, J, Ballerini, P, Lapillonne, H, Van der Velden, V H J; https://orcid.org/0000-0001-9457-3763, Sonneveld, E, Delabesse, E, de Matos, R R C; https://orcid.org/0000-0002-8737-1669, Silva, M L M; https://orcid.org/0000-0003-2549-1320, Bomken, S; https://orcid.org/0000-0001-9163-5738, Katsibardi, K, Keernik, M, Schäfer, Beat W; https://orcid.org/0000-0001-5988-2915, and et al

Abstract

Chromosomal rearrangements of the human KMT2A/MLL gene are associated with de novo as well as therapy-induced infant, pediatric, and adult acute leukemias. Here, we present the data obtained from 3401 acute leukemia patients that have been analyzed between 2003 and 2022. Genomic breakpoints within the KMT2A gene and the involved translocation partner genes (TPGs) and KMT2A-partial tandem duplications (PTDs) were determined. Including the published data from the literature, a total of 107 in-frame KMT2A gene fusions have been identified so far. Further 16 rearrangements were out-of-frame fusions, 18 patients had no partner gene fused to 5'-KMT2A, two patients had a 5'-KMT2A deletion, and one ETV6::RUNX1 patient had an KMT2A insertion at the breakpoint. The seven most frequent TPGs and PTDs account for more than 90% of all recombinations of the KMT2A, 37 occur recurrently and 63 were identified so far only once. This study provides a comprehensive analysis of the KMT2A recombinome in acute leukemia patients. Besides the scientific gain of information, genomic breakpoint sequences of these patients were used to monitor minimal residual disease (MRD). Thus, this work may be directly translated from the bench to the bedside of patients and meet the clinical needs to improve patient survival.

Published
2023

2. 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

3. 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

4. The MLL recombinome of acute leukemias in 2017

Author

Elena Zerkalenkova, A Bidet, Anatoly Kustanovich, C Barbieri Blunck, Hans O. Madsen, Jeremy Hancock, Sabine Strehl, Hélène Cavé, Beat W. Schäfer, Aurélie Caye, Jana Lentes, L Corral Abascal, Giovanni Cazzaniga, B Almeida Lopes, M. De Braekeleer, Eric Lippert, Aline Renneville, Grigory Tsaur, Julia Alten, Oskar A. Haas, Lukasz Sedek, Eric Delabesse, Martin Stanulla, Maria Luiza Macedo Silva, Emmanuelle Clappier, Anja Möricke, Christian Meyer, Mariana Emerenciano, Martin Schrappe, Hélène Lapillonne, Rosemary Sutton, Thomas Burmeister, Rolf Marschalek, Michael Dworzak, T Lund-Aho, V H J van der Velden, Clara Bueno, Paola Ballerini, Jan Trka, Maria S. Pombo-de-Oliveira, Yulia Olshanskaya, Daniela Gröger, Shai Izraeli, Olga Aleinikova, Gudrun Göhring, Vesa Juvonen, Andishe Attarbaschi, Nicola C. Venn, S Kubetzko, J M Cayuela, Andrew S. Moore, T S Park, Paula Gameiro, S H Oh, Christian M. Zwaan, Renate Panzer-Grümayer, L Suarez, X Duarte, Josef Vormoor, Olaf Heidenreich, P Archer, Pablo Menendez, Bernd Gruhn, Jan Zuna, Cristina N. Alonso, M M van den Heuvel-Eibrink, Andrea Teigler-Schlegel, L. Trakhtenbrot, U zur Stadt, L Fechina, Tomasz Szczepański, Immunology, Pediatrics, 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, and Marschalek, R

Subjects
0301 basic medicine, Adult, Male, Cancer Research, MED/03 - GENETICA MEDICA, Oncogene Proteins, Fusion, Chromosome Aberration, Translocation, Genetic, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, medicine, Humans, Child, neoplasms, Genetics, Chromosome Aberrations, Gene Rearrangement, Acute leukemia, biology, Breakpoint, Infant, Chromosome Breakage, Hematology, Gene rearrangement, Histone-Lysine N-Methyltransferase, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, ta3122, Minimal residual disease, 3. Good health, Leukemia, Leukemia, Myeloid, Acute, 030104 developmental biology, KMT2A, Oncology, 030220 oncology & carcinogenesis, biology.protein, Myeloid-Lymphoid Leukemia Protein, Original Article, Female, Chromosome breakage, Human
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

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