CNL and aCML should be considered as a single entity based on molecular profiles and outcomes
Gonzalo Carreño‐Tarragona, Alberto Álvarez‐Larrán, Claire Harrison, José Carlos Martínez Ávila, Juan Carlos Hernández‐Boluda, Francisca Ferrer‐Marín, Deepti Radia, Elvira Mora, Sebastian Francis, Teresa González‐Martínez, Kathryn Goddard, Manuel Pérez‐Encinas, Srinivasan Narayanan, José María Raya, Vikram Singh, Xabier Gutiérrez, Peter P. Tóth, Paula Amat-Martínez, Louisa McIlwaine, Magda Alobaidi, Karan Mayani‐Mayani, Andrew McGregor, Ruth Stuckey, Bethan Psaila, Adrián Segura, Caroline Alvares, Kerri Davidson, Santiago Osorio, Robert Cutting, Caroline P. Sweeney, Laura Rufián, Laura Moreno‐Galarraga, Isabel Cuenca, Jeffery Smith, María Luz Morales, Rodrigo Gil-Manso, Ioannis Koutsavlis, Lihui Wang, Adam J. Mead, Marı́a Rozman, Joaquín Martínez‐López, Rosa Ayala, Nicholas C.P. Cross
Abstract
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.