CNL and aCML should be considered as single entity based on molecular profiles and outcomes.
Gonzalo Carreno-TarragonaAlberto Alvarez-LarranClaire N HarrisonJose Carlos Martínez ÁvilaJuan Carlos Carlos Hernández-BoludaFrancisca Ferrer-MarínDeepti H RadiaElvira Mora CasteráSebastian FrancisTeresa González-MartínezKathryn GoddardManuel Mateo Pérez EncinasSrinivasan NarayananJose Maria RayaVikram SinghPeter TothXabier GutiérrezPaula Amat MartinezLouisa McIlwaineMagda AlobaidiKaran MayaniAndrew McGregorRuth StuckeyBethan PsailaAdrian SeguraCaroline L AlvaresKerri DavidsonSantiago OsorioRobert CuttingCaroline P SweeneyLaura RufianLaura MorenoIsabel CuencaJeffrey SmithMaria Luz MoralesRodrigo Gil-MansoIoannis KoutsavlisLihui WangAdam J MeadMaria RozmanJoaquin Martínez-LópezRosa María AyalaNicholas C P CrossPublished in: Blood advances (2022)
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 of these disorders we undertook a multi-center 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 presentation or outcomes between 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 (MDS/MPN). We identified four high-risk mutated genes, specifically CEBPA (β=2.26, HR=9.54, p=0.003), EZH2 (β=1.12, HR=3.062, p=0.009), NRAS (β=1.29, HR=3.63, p=0.048) and U2AF1 (β=1.75, HR=5.74, p=0.013) by 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.
Keyphrases
- acute myeloid leukemia
- bone marrow
- signaling pathway
- single molecule
- dendritic cells
- atrial fibrillation
- gene expression
- oxidative stress
- transcription factor
- deep learning
- type diabetes
- metabolic syndrome
- electronic health record
- dna methylation
- genome wide
- immune response
- epithelial mesenchymal transition
- wild type
- cerebrospinal fluid
- weight loss
- induced apoptosis
- pi k akt