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Myeloid malignancies with translocation t(4;12)(q11‐13;p13): molecular landscape, clonal hierarchy and clinical outcomes

Translocation t(4;12)(q11‐13;p13) is a recurrent but very rare chromosomal aberration in acute myeloid leukaemia (AML) resulting in the non‐constant expression of a CHIC2/ETV6 fusion transcript. We report clinico‐biological features, molecular characteristics and outcomes of 21 cases of t(4;12) incl...

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Autores principales: Parinet, Vincent, Chapiro, Elise, Bidet, Audrey, Gaillard, Baptiste, Maarek, Odile, Simon, Laurence, Lefebvre, Christine, Defasque, Sabine, Mozziconacci, Marie‐Joelle, Quinquenel, Anne, Decamp, Matthieu, Lifermann, François, Ali‐Ammar, Nadia, Maillon, Agathe, Baron, Marine, Martin, Mélanie, Struski, Stéphanie, Penther, Dominique, Micol, Jean‐Baptiste, Auger, Nathalie, Bilhou‐Nabera, Chrystèle, Martignoles, Jean‐Alain, Tondeur, Sylvie, Nguyen‐Khac, Florence, Hirsch, Pierre, Roos‐Weil, Damien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505829/
https://www.ncbi.nlm.nih.gov/pubmed/34492730
http://dx.doi.org/10.1111/jcmm.16895
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author Parinet, Vincent
Chapiro, Elise
Bidet, Audrey
Gaillard, Baptiste
Maarek, Odile
Simon, Laurence
Lefebvre, Christine
Defasque, Sabine
Mozziconacci, Marie‐Joelle
Quinquenel, Anne
Decamp, Matthieu
Lifermann, François
Ali‐Ammar, Nadia
Maillon, Agathe
Baron, Marine
Martin, Mélanie
Struski, Stéphanie
Penther, Dominique
Micol, Jean‐Baptiste
Auger, Nathalie
Bilhou‐Nabera, Chrystèle
Martignoles, Jean‐Alain
Tondeur, Sylvie
Nguyen‐Khac, Florence
Hirsch, Pierre
Roos‐Weil, Damien
author_facet Parinet, Vincent
Chapiro, Elise
Bidet, Audrey
Gaillard, Baptiste
Maarek, Odile
Simon, Laurence
Lefebvre, Christine
Defasque, Sabine
Mozziconacci, Marie‐Joelle
Quinquenel, Anne
Decamp, Matthieu
Lifermann, François
Ali‐Ammar, Nadia
Maillon, Agathe
Baron, Marine
Martin, Mélanie
Struski, Stéphanie
Penther, Dominique
Micol, Jean‐Baptiste
Auger, Nathalie
Bilhou‐Nabera, Chrystèle
Martignoles, Jean‐Alain
Tondeur, Sylvie
Nguyen‐Khac, Florence
Hirsch, Pierre
Roos‐Weil, Damien
author_sort Parinet, Vincent
collection PubMed
description Translocation t(4;12)(q11‐13;p13) is a recurrent but very rare chromosomal aberration in acute myeloid leukaemia (AML) resulting in the non‐constant expression of a CHIC2/ETV6 fusion transcript. We report clinico‐biological features, molecular characteristics and outcomes of 21 cases of t(4;12) including 19 AML and two myelodysplastic syndromes (MDS). Median age at the time of t(4;12) was 78 years (range, 56–88). Multilineage dysplasia was described in 10 of 19 (53%) AML cases and CD7 and/or CD56 expression in 90%. FISH analyses identified ETV6 and CHIC2 region rearrangements in respectively 18 of 18 and 15 of 17 studied cases. The t(4;12) was the sole cytogenetic abnormality in 48% of cases. The most frequent associated mutated genes were ASXL1 (n = 8/16, 50%), IDH1/2 (n = 7/16, 44%), SRSF2 (n = 5/16, 31%) and RUNX1 (n = 4/16, 25%). Interestingly, concurrent FISH and molecular analyses showed that t(4;12) can be, but not always, a founding oncogenic event. Median OS was 7.8 months for the entire cohort. In the 16 of 21 patients (76%) who received antitumoral treatment, overall response and first complete remission rates were 37% and 31%, respectively. Median progression‐free survival in responders was 13.7 months. Finally, t(4;12) cases harboured many characteristics of AML with myelodysplasia‐related changes (multilineage dysplasia, MDS‐related cytogenetic abnormalities, frequent ASXL1 mutations) and a poor prognosis.
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spelling pubmed-85058292021-10-18 Myeloid malignancies with translocation t(4;12)(q11‐13;p13): molecular landscape, clonal hierarchy and clinical outcomes Parinet, Vincent Chapiro, Elise Bidet, Audrey Gaillard, Baptiste Maarek, Odile Simon, Laurence Lefebvre, Christine Defasque, Sabine Mozziconacci, Marie‐Joelle Quinquenel, Anne Decamp, Matthieu Lifermann, François Ali‐Ammar, Nadia Maillon, Agathe Baron, Marine Martin, Mélanie Struski, Stéphanie Penther, Dominique Micol, Jean‐Baptiste Auger, Nathalie Bilhou‐Nabera, Chrystèle Martignoles, Jean‐Alain Tondeur, Sylvie Nguyen‐Khac, Florence Hirsch, Pierre Roos‐Weil, Damien J Cell Mol Med Original Articles Translocation t(4;12)(q11‐13;p13) is a recurrent but very rare chromosomal aberration in acute myeloid leukaemia (AML) resulting in the non‐constant expression of a CHIC2/ETV6 fusion transcript. We report clinico‐biological features, molecular characteristics and outcomes of 21 cases of t(4;12) including 19 AML and two myelodysplastic syndromes (MDS). Median age at the time of t(4;12) was 78 years (range, 56–88). Multilineage dysplasia was described in 10 of 19 (53%) AML cases and CD7 and/or CD56 expression in 90%. FISH analyses identified ETV6 and CHIC2 region rearrangements in respectively 18 of 18 and 15 of 17 studied cases. The t(4;12) was the sole cytogenetic abnormality in 48% of cases. The most frequent associated mutated genes were ASXL1 (n = 8/16, 50%), IDH1/2 (n = 7/16, 44%), SRSF2 (n = 5/16, 31%) and RUNX1 (n = 4/16, 25%). Interestingly, concurrent FISH and molecular analyses showed that t(4;12) can be, but not always, a founding oncogenic event. Median OS was 7.8 months for the entire cohort. In the 16 of 21 patients (76%) who received antitumoral treatment, overall response and first complete remission rates were 37% and 31%, respectively. Median progression‐free survival in responders was 13.7 months. Finally, t(4;12) cases harboured many characteristics of AML with myelodysplasia‐related changes (multilineage dysplasia, MDS‐related cytogenetic abnormalities, frequent ASXL1 mutations) and a poor prognosis. John Wiley and Sons Inc. 2021-09-07 2021-10 /pmc/articles/PMC8505829/ /pubmed/34492730 http://dx.doi.org/10.1111/jcmm.16895 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Parinet, Vincent
Chapiro, Elise
Bidet, Audrey
Gaillard, Baptiste
Maarek, Odile
Simon, Laurence
Lefebvre, Christine
Defasque, Sabine
Mozziconacci, Marie‐Joelle
Quinquenel, Anne
Decamp, Matthieu
Lifermann, François
Ali‐Ammar, Nadia
Maillon, Agathe
Baron, Marine
Martin, Mélanie
Struski, Stéphanie
Penther, Dominique
Micol, Jean‐Baptiste
Auger, Nathalie
Bilhou‐Nabera, Chrystèle
Martignoles, Jean‐Alain
Tondeur, Sylvie
Nguyen‐Khac, Florence
Hirsch, Pierre
Roos‐Weil, Damien
Myeloid malignancies with translocation t(4;12)(q11‐13;p13): molecular landscape, clonal hierarchy and clinical outcomes
title Myeloid malignancies with translocation t(4;12)(q11‐13;p13): molecular landscape, clonal hierarchy and clinical outcomes
title_full Myeloid malignancies with translocation t(4;12)(q11‐13;p13): molecular landscape, clonal hierarchy and clinical outcomes
title_fullStr Myeloid malignancies with translocation t(4;12)(q11‐13;p13): molecular landscape, clonal hierarchy and clinical outcomes
title_full_unstemmed Myeloid malignancies with translocation t(4;12)(q11‐13;p13): molecular landscape, clonal hierarchy and clinical outcomes
title_short Myeloid malignancies with translocation t(4;12)(q11‐13;p13): molecular landscape, clonal hierarchy and clinical outcomes
title_sort myeloid malignancies with translocation t(4;12)(q11‐13;p13): molecular landscape, clonal hierarchy and clinical outcomes
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505829/
https://www.ncbi.nlm.nih.gov/pubmed/34492730
http://dx.doi.org/10.1111/jcmm.16895
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