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CNL and aCML should be considered as a single entity based on molecular profiles and outcomes
Chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) are rare myeloid disorders that are challenging with regard to diagnosis and clinical management. To study the similarities and differences between these disorders, we undertook a multicenter international study of one...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society of Hematology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10182308/ https://www.ncbi.nlm.nih.gov/pubmed/36375042 http://dx.doi.org/10.1182/bloodadvances.2022008204 |
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author | Carreño-Tarragona, Gonzalo Álvarez-Larrán, Alberto Harrison, Claire Martínez-Ávila, José Carlos Hernández-Boluda, Juan Carlos Ferrer-Marín, Francisca Radia, Deepti H. Mora, Elvira Francis, Sebastian González-Martínez, Teresa Goddard, Kathryn Pérez-Encinas, Manuel Narayanan, Srinivasan Raya, José María Singh, Vikram Gutiérrez, Xabier Toth, Peter Amat-Martínez, Paula Mcilwaine, Louisa Alobaidi, Magda Mayani, Karan McGregor, Andrew Stuckey, Ruth Psaila, Bethan Segura, Adrián Alvares, Caroline Davidson, Kerri Osorio, Santiago Cutting, Robert Sweeney, Caroline P. Rufián, Laura Moreno, Laura Cuenca, Isabel Smith, Jeffery Morales, María Luz Gil-Manso, Rodrigo Koutsavlis, Ioannis Wang, Lihui Mead, Adam J. Rozman, María Martínez-López, Joaquín Ayala, Rosa Cross, Nicholas C. P. |
author_facet | Carreño-Tarragona, Gonzalo Álvarez-Larrán, Alberto Harrison, Claire Martínez-Ávila, José Carlos Hernández-Boluda, Juan Carlos Ferrer-Marín, Francisca Radia, Deepti H. Mora, Elvira Francis, Sebastian González-Martínez, Teresa Goddard, Kathryn Pérez-Encinas, Manuel Narayanan, Srinivasan Raya, José María Singh, Vikram Gutiérrez, Xabier Toth, Peter Amat-Martínez, Paula Mcilwaine, Louisa Alobaidi, Magda Mayani, Karan McGregor, Andrew Stuckey, Ruth Psaila, Bethan Segura, Adrián Alvares, Caroline Davidson, Kerri Osorio, Santiago Cutting, Robert Sweeney, Caroline P. Rufián, Laura Moreno, Laura Cuenca, Isabel Smith, Jeffery Morales, María Luz Gil-Manso, Rodrigo Koutsavlis, Ioannis Wang, Lihui Mead, Adam J. Rozman, María Martínez-López, Joaquín Ayala, Rosa Cross, Nicholas C. P. |
author_sort | Carreño-Tarragona, Gonzalo |
collection | PubMed |
description | Chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) are rare myeloid disorders that are challenging with regard to diagnosis and clinical management. To study the similarities and differences between these disorders, we undertook a multicenter international study of one of the largest case series (CNL, n = 24; aCML, n = 37 cases, respectively), focusing on the clinical and mutational profiles (n = 53 with molecular data) of these diseases. We found no differences in clinical presentations or outcomes of both entities. As previously described, both CNL and aCML share a complex mutational profile with mutations in genes involved in epigenetic regulation, splicing, and signaling pathways. Apart from CSF3R, only EZH2 and TET2 were differentially mutated between them. The molecular profiles support the notion of CNL and aCML being a continuum of the same disease that may fit best within the myelodysplastic/myeloproliferative neoplasms. We identified 4 high-risk mutated genes, specifically CEBPA (β = 2.26, hazard ratio [HR] = 9.54, P = .003), EZH2 (β = 1.12, HR = 3.062, P = .009), NRAS (β = 1.29, HR = 3.63, P = .048), and U2AF1 (β = 1.75, HR = 5.74, P = .013) using multivariate analysis. Our findings underscore the relevance of molecular-risk classification in CNL/aCML as well as the importance of CSF3R mutations in these diseases. |
format | Online Article Text |
id | pubmed-10182308 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-101823082023-05-14 CNL and aCML should be considered as a single entity based on molecular profiles and outcomes Carreño-Tarragona, Gonzalo Álvarez-Larrán, Alberto Harrison, Claire Martínez-Ávila, José Carlos Hernández-Boluda, Juan Carlos Ferrer-Marín, Francisca Radia, Deepti H. Mora, Elvira Francis, Sebastian González-Martínez, Teresa Goddard, Kathryn Pérez-Encinas, Manuel Narayanan, Srinivasan Raya, José María Singh, Vikram Gutiérrez, Xabier Toth, Peter Amat-Martínez, Paula Mcilwaine, Louisa Alobaidi, Magda Mayani, Karan McGregor, Andrew Stuckey, Ruth Psaila, Bethan Segura, Adrián Alvares, Caroline Davidson, Kerri Osorio, Santiago Cutting, Robert Sweeney, Caroline P. Rufián, Laura Moreno, Laura Cuenca, Isabel Smith, Jeffery Morales, María Luz Gil-Manso, Rodrigo Koutsavlis, Ioannis Wang, Lihui Mead, Adam J. Rozman, María Martínez-López, Joaquín Ayala, Rosa Cross, Nicholas C. P. Blood Adv Myeloid Neoplasia Chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) are rare myeloid disorders that are challenging with regard to diagnosis and clinical management. To study the similarities and differences between these disorders, we undertook a multicenter international study of one of the largest case series (CNL, n = 24; aCML, n = 37 cases, respectively), focusing on the clinical and mutational profiles (n = 53 with molecular data) of these diseases. We found no differences in clinical presentations or outcomes of both entities. As previously described, both CNL and aCML share a complex mutational profile with mutations in genes involved in epigenetic regulation, splicing, and signaling pathways. Apart from CSF3R, only EZH2 and TET2 were differentially mutated between them. The molecular profiles support the notion of CNL and aCML being a continuum of the same disease that may fit best within the myelodysplastic/myeloproliferative neoplasms. We identified 4 high-risk mutated genes, specifically CEBPA (β = 2.26, hazard ratio [HR] = 9.54, P = .003), EZH2 (β = 1.12, HR = 3.062, P = .009), NRAS (β = 1.29, HR = 3.63, P = .048), and U2AF1 (β = 1.75, HR = 5.74, P = .013) using multivariate analysis. Our findings underscore the relevance of molecular-risk classification in CNL/aCML as well as the importance of CSF3R mutations in these diseases. The American Society of Hematology 2022-11-16 /pmc/articles/PMC10182308/ /pubmed/36375042 http://dx.doi.org/10.1182/bloodadvances.2022008204 Text en © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Myeloid Neoplasia Carreño-Tarragona, Gonzalo Álvarez-Larrán, Alberto Harrison, Claire Martínez-Ávila, José Carlos Hernández-Boluda, Juan Carlos Ferrer-Marín, Francisca Radia, Deepti H. Mora, Elvira Francis, Sebastian González-Martínez, Teresa Goddard, Kathryn Pérez-Encinas, Manuel Narayanan, Srinivasan Raya, José María Singh, Vikram Gutiérrez, Xabier Toth, Peter Amat-Martínez, Paula Mcilwaine, Louisa Alobaidi, Magda Mayani, Karan McGregor, Andrew Stuckey, Ruth Psaila, Bethan Segura, Adrián Alvares, Caroline Davidson, Kerri Osorio, Santiago Cutting, Robert Sweeney, Caroline P. Rufián, Laura Moreno, Laura Cuenca, Isabel Smith, Jeffery Morales, María Luz Gil-Manso, Rodrigo Koutsavlis, Ioannis Wang, Lihui Mead, Adam J. Rozman, María Martínez-López, Joaquín Ayala, Rosa Cross, Nicholas C. P. CNL and aCML should be considered as a single entity based on molecular profiles and outcomes |
title | CNL and aCML should be considered as a single entity based on molecular profiles and outcomes |
title_full | CNL and aCML should be considered as a single entity based on molecular profiles and outcomes |
title_fullStr | CNL and aCML should be considered as a single entity based on molecular profiles and outcomes |
title_full_unstemmed | CNL and aCML should be considered as a single entity based on molecular profiles and outcomes |
title_short | CNL and aCML should be considered as a single entity based on molecular profiles and outcomes |
title_sort | cnl and acml should be considered as a single entity based on molecular profiles and outcomes |
topic | Myeloid Neoplasia |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10182308/ https://www.ncbi.nlm.nih.gov/pubmed/36375042 http://dx.doi.org/10.1182/bloodadvances.2022008204 |
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