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Molecular Landscape of Therapy-related Myeloid Neoplasms in Patients Previously Treated for Gynecologic and Breast Cancers
Definition of therapy-related myeloid neoplasms (TRMN) is only based on clinical history of exposure to leukemogenic therapy. No specific molecular classification combining therapy-related acute myeloid leukemia and therapy-related myelodysplastic syndromes has been proposed. We aimed to describe th...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373540/ https://www.ncbi.nlm.nih.gov/pubmed/34423258 http://dx.doi.org/10.1097/HS9.0000000000000632 |
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author | Khalife-Hachem, Sabine Saleh, Khalil Pasquier, Florence Willekens, Christophe Tarabay, Anthony Antoun, Leony Grinda, Thomas Castilla-Llorente, Cristina Duchmann, Matthieu Quivoron, Cyril Auger, Nathalie Saada, Veronique Delaloge, Suzette Leary, Alexandra Renneville, Aline Antony-Debre, Ileana Rosselli, Filippo De Botton, Stéphane Salviat, Flore Marzac, Christophe Micol, Jean-Baptiste |
author_facet | Khalife-Hachem, Sabine Saleh, Khalil Pasquier, Florence Willekens, Christophe Tarabay, Anthony Antoun, Leony Grinda, Thomas Castilla-Llorente, Cristina Duchmann, Matthieu Quivoron, Cyril Auger, Nathalie Saada, Veronique Delaloge, Suzette Leary, Alexandra Renneville, Aline Antony-Debre, Ileana Rosselli, Filippo De Botton, Stéphane Salviat, Flore Marzac, Christophe Micol, Jean-Baptiste |
author_sort | Khalife-Hachem, Sabine |
collection | PubMed |
description | Definition of therapy-related myeloid neoplasms (TRMN) is only based on clinical history of exposure to leukemogenic therapy. No specific molecular classification combining therapy-related acute myeloid leukemia and therapy-related myelodysplastic syndromes has been proposed. We aimed to describe the molecular landscape of TRMN at diagnosis, among 77 patients with previous gynecologic and breast cancer with a dedicated next-generation sequencing panel covering 74 genes. We investigated the impact of clonal hematopoiesis of indeterminate potential-associated mutations (CHIP-AMs defined as presence at TRMN stage of mutations described in CHIP with a frequency >1%) on overall survival (OS) and the clinical relevance of a modified genetic ontogeny-based classifier that categorized patients in 3 subgroups. The most frequently mutated genes were TP53 (31%), DNMT3A (19%), IDH1/2 (13%), NRAS (13%), TET2 (12%), NPM1 (10%), PPM1D (9%), and PTPN11 (9%). CHIP-AMs were detected in 66% of TRMN patients, with no impact on OS. Yet, patients with CHIP-AM were older and had a longer time interval between solid tumor diagnosis and TRMN. According to our modified ontogeny-based classifier, we observed that the patients with TP53 or PPM1D mutations had more treatment lines and complex karyotypes, the “MDS-like” patients were older with more gene mutations, while patients with “De novo/pan-AML” mutations were younger with more balanced chromosomal translocations. Median OS within each subgroup was 7.5, 14.5, and 25.2 months, respectively, with statistically significant difference in multivariate analysis. These results support the integration of cytogenetic and molecular markers into the future TRMN classification to reflect the biological diversity of TRMN and its impact on outcomes. |
format | Online Article Text |
id | pubmed-8373540 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-83735402021-08-20 Molecular Landscape of Therapy-related Myeloid Neoplasms in Patients Previously Treated for Gynecologic and Breast Cancers Khalife-Hachem, Sabine Saleh, Khalil Pasquier, Florence Willekens, Christophe Tarabay, Anthony Antoun, Leony Grinda, Thomas Castilla-Llorente, Cristina Duchmann, Matthieu Quivoron, Cyril Auger, Nathalie Saada, Veronique Delaloge, Suzette Leary, Alexandra Renneville, Aline Antony-Debre, Ileana Rosselli, Filippo De Botton, Stéphane Salviat, Flore Marzac, Christophe Micol, Jean-Baptiste Hemasphere Article Definition of therapy-related myeloid neoplasms (TRMN) is only based on clinical history of exposure to leukemogenic therapy. No specific molecular classification combining therapy-related acute myeloid leukemia and therapy-related myelodysplastic syndromes has been proposed. We aimed to describe the molecular landscape of TRMN at diagnosis, among 77 patients with previous gynecologic and breast cancer with a dedicated next-generation sequencing panel covering 74 genes. We investigated the impact of clonal hematopoiesis of indeterminate potential-associated mutations (CHIP-AMs defined as presence at TRMN stage of mutations described in CHIP with a frequency >1%) on overall survival (OS) and the clinical relevance of a modified genetic ontogeny-based classifier that categorized patients in 3 subgroups. The most frequently mutated genes were TP53 (31%), DNMT3A (19%), IDH1/2 (13%), NRAS (13%), TET2 (12%), NPM1 (10%), PPM1D (9%), and PTPN11 (9%). CHIP-AMs were detected in 66% of TRMN patients, with no impact on OS. Yet, patients with CHIP-AM were older and had a longer time interval between solid tumor diagnosis and TRMN. According to our modified ontogeny-based classifier, we observed that the patients with TP53 or PPM1D mutations had more treatment lines and complex karyotypes, the “MDS-like” patients were older with more gene mutations, while patients with “De novo/pan-AML” mutations were younger with more balanced chromosomal translocations. Median OS within each subgroup was 7.5, 14.5, and 25.2 months, respectively, with statistically significant difference in multivariate analysis. These results support the integration of cytogenetic and molecular markers into the future TRMN classification to reflect the biological diversity of TRMN and its impact on outcomes. Lippincott Williams & Wilkins 2021-08-18 /pmc/articles/PMC8373540/ /pubmed/34423258 http://dx.doi.org/10.1097/HS9.0000000000000632 Text en Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY) (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Article Khalife-Hachem, Sabine Saleh, Khalil Pasquier, Florence Willekens, Christophe Tarabay, Anthony Antoun, Leony Grinda, Thomas Castilla-Llorente, Cristina Duchmann, Matthieu Quivoron, Cyril Auger, Nathalie Saada, Veronique Delaloge, Suzette Leary, Alexandra Renneville, Aline Antony-Debre, Ileana Rosselli, Filippo De Botton, Stéphane Salviat, Flore Marzac, Christophe Micol, Jean-Baptiste Molecular Landscape of Therapy-related Myeloid Neoplasms in Patients Previously Treated for Gynecologic and Breast Cancers |
title | Molecular Landscape of Therapy-related Myeloid Neoplasms in Patients Previously Treated for Gynecologic and Breast Cancers |
title_full | Molecular Landscape of Therapy-related Myeloid Neoplasms in Patients Previously Treated for Gynecologic and Breast Cancers |
title_fullStr | Molecular Landscape of Therapy-related Myeloid Neoplasms in Patients Previously Treated for Gynecologic and Breast Cancers |
title_full_unstemmed | Molecular Landscape of Therapy-related Myeloid Neoplasms in Patients Previously Treated for Gynecologic and Breast Cancers |
title_short | Molecular Landscape of Therapy-related Myeloid Neoplasms in Patients Previously Treated for Gynecologic and Breast Cancers |
title_sort | molecular landscape of therapy-related myeloid neoplasms in patients previously treated for gynecologic and breast cancers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373540/ https://www.ncbi.nlm.nih.gov/pubmed/34423258 http://dx.doi.org/10.1097/HS9.0000000000000632 |
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