CNL and aCML should be considered as a single entity based on molecular profiles and outcomes.
Многоцентровое исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.