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Clonally unrelated Richter syndrome are truly de novo diffuse large B‐cell lymphomas with a mutational profile reminiscent of clonally related Richter syndrome
Richter syndrome (RS) is mostly due to the direct transformation of the chronic lymphocytic leukaemia (CLL) clone, as documented by the same immunoglobulin heavy‐chain variable region (IGHV) rearrangement in both CLL and RS cells. In rare cases characterized by a better outcome, the RS clone harbour...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9543999/ https://www.ncbi.nlm.nih.gov/pubmed/35829664 http://dx.doi.org/10.1111/bjh.18352 |
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author | Favini, Chiara Talotta, Donatella Almasri, Mohammad Andorno, Annalisa Rasi, Silvia Adhinaveni, Ramesh Kogila, Sreekar Awikeh, Bassel Schipani, Mattia Boggione, Paola Mouhssine, Samir Ghanej, Joseph Al Essa, Wael Mahmoud, Abdurraouf Mokhtar Dondolin, Riccardo Alessa, Nariman Margiotta Casaluci, Gloria Boldorini, Renzo Gattei, Valter Gaidano, Gianluca Moia, Riccardo |
author_facet | Favini, Chiara Talotta, Donatella Almasri, Mohammad Andorno, Annalisa Rasi, Silvia Adhinaveni, Ramesh Kogila, Sreekar Awikeh, Bassel Schipani, Mattia Boggione, Paola Mouhssine, Samir Ghanej, Joseph Al Essa, Wael Mahmoud, Abdurraouf Mokhtar Dondolin, Riccardo Alessa, Nariman Margiotta Casaluci, Gloria Boldorini, Renzo Gattei, Valter Gaidano, Gianluca Moia, Riccardo |
author_sort | Favini, Chiara |
collection | PubMed |
description | Richter syndrome (RS) is mostly due to the direct transformation of the chronic lymphocytic leukaemia (CLL) clone, as documented by the same immunoglobulin heavy‐chain variable region (IGHV) rearrangement in both CLL and RS cells. In rare cases characterized by a better outcome, the RS clone harbours a different IGHV rearrangement compared to the CLL phase. We investigated the CLL phase of clonally unrelated RS to test whether the RS clone was already identifiable prior to clinicopathologic transformation, albeit undetectable by conventional approaches. CLL cells of eight patients with unrelated RS were subjected to an ultra‐deep next‐generation sequencing (NGS) approach with a sensitivity of 10(−6). In 7/8 cases, the RS rearrangement was not identified in the CLL phase. In one case, the RS clone was identified at a very low frequency in the CLL phase, conceivably due to the concomitance of CLL sampling and RS diagnosis. Targeted resequencing revealed that clonally unrelated RS carries genetic lesions primarily affecting the TP53, MYC, ATM and NOTCH1 genes. Conversely, mutations frequently involved in de novo diffuse large B‐cell lymphoma (DLBCL) without a history of CLL were absent. These results suggest that clonally unrelated RS is a truly de novo lymphoma with a mutational profile reminiscent, at least in part, of clonally related RS. |
format | Online Article Text |
id | pubmed-9543999 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95439992022-10-14 Clonally unrelated Richter syndrome are truly de novo diffuse large B‐cell lymphomas with a mutational profile reminiscent of clonally related Richter syndrome Favini, Chiara Talotta, Donatella Almasri, Mohammad Andorno, Annalisa Rasi, Silvia Adhinaveni, Ramesh Kogila, Sreekar Awikeh, Bassel Schipani, Mattia Boggione, Paola Mouhssine, Samir Ghanej, Joseph Al Essa, Wael Mahmoud, Abdurraouf Mokhtar Dondolin, Riccardo Alessa, Nariman Margiotta Casaluci, Gloria Boldorini, Renzo Gattei, Valter Gaidano, Gianluca Moia, Riccardo Br J Haematol Haematological Malignancy–Biology Richter syndrome (RS) is mostly due to the direct transformation of the chronic lymphocytic leukaemia (CLL) clone, as documented by the same immunoglobulin heavy‐chain variable region (IGHV) rearrangement in both CLL and RS cells. In rare cases characterized by a better outcome, the RS clone harbours a different IGHV rearrangement compared to the CLL phase. We investigated the CLL phase of clonally unrelated RS to test whether the RS clone was already identifiable prior to clinicopathologic transformation, albeit undetectable by conventional approaches. CLL cells of eight patients with unrelated RS were subjected to an ultra‐deep next‐generation sequencing (NGS) approach with a sensitivity of 10(−6). In 7/8 cases, the RS rearrangement was not identified in the CLL phase. In one case, the RS clone was identified at a very low frequency in the CLL phase, conceivably due to the concomitance of CLL sampling and RS diagnosis. Targeted resequencing revealed that clonally unrelated RS carries genetic lesions primarily affecting the TP53, MYC, ATM and NOTCH1 genes. Conversely, mutations frequently involved in de novo diffuse large B‐cell lymphoma (DLBCL) without a history of CLL were absent. These results suggest that clonally unrelated RS is a truly de novo lymphoma with a mutational profile reminiscent, at least in part, of clonally related RS. John Wiley and Sons Inc. 2022-07-13 2022-09 /pmc/articles/PMC9543999/ /pubmed/35829664 http://dx.doi.org/10.1111/bjh.18352 Text en © 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Haematological Malignancy–Biology Favini, Chiara Talotta, Donatella Almasri, Mohammad Andorno, Annalisa Rasi, Silvia Adhinaveni, Ramesh Kogila, Sreekar Awikeh, Bassel Schipani, Mattia Boggione, Paola Mouhssine, Samir Ghanej, Joseph Al Essa, Wael Mahmoud, Abdurraouf Mokhtar Dondolin, Riccardo Alessa, Nariman Margiotta Casaluci, Gloria Boldorini, Renzo Gattei, Valter Gaidano, Gianluca Moia, Riccardo Clonally unrelated Richter syndrome are truly de novo diffuse large B‐cell lymphomas with a mutational profile reminiscent of clonally related Richter syndrome |
title | Clonally unrelated Richter syndrome are truly de novo diffuse large B‐cell lymphomas with a mutational profile reminiscent of clonally related Richter syndrome |
title_full | Clonally unrelated Richter syndrome are truly de novo diffuse large B‐cell lymphomas with a mutational profile reminiscent of clonally related Richter syndrome |
title_fullStr | Clonally unrelated Richter syndrome are truly de novo diffuse large B‐cell lymphomas with a mutational profile reminiscent of clonally related Richter syndrome |
title_full_unstemmed | Clonally unrelated Richter syndrome are truly de novo diffuse large B‐cell lymphomas with a mutational profile reminiscent of clonally related Richter syndrome |
title_short | Clonally unrelated Richter syndrome are truly de novo diffuse large B‐cell lymphomas with a mutational profile reminiscent of clonally related Richter syndrome |
title_sort | clonally unrelated richter syndrome are truly de novo diffuse large b‐cell lymphomas with a mutational profile reminiscent of clonally related richter syndrome |
topic | Haematological Malignancy–Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9543999/ https://www.ncbi.nlm.nih.gov/pubmed/35829664 http://dx.doi.org/10.1111/bjh.18352 |
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