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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society of Hematology 2022
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.
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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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