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CNL and aCML should be considered as a single entity based on molecular profiles and outcomes

2023· article· en· W4309098190 on OpenAlexfundno aff
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

Bibliographic record

VenueBlood Advances · 2023
Typearticle
Languageen
FieldMedicine
TopicAcute Myeloid Leukemia Research
Canadian institutionsnot available
FundersInstituto de Salud Carlos IIIAstellas PharmaAcademy of Medical SciencesCancer Research UKGalectoSierra OncologyCTI BiopharmaIncyteWellcome TrustCelgeneGilead SciencesNational Institute for Health and Care ResearchJazz PharmaceuticalsEuropean Hematology AssociationBristol-Myers Squibb
KeywordsMedicine

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.005
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.005
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0020.001
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.042
GPT teacher head0.343
Teacher spread0.301 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations31
Published2023
Admission routes1
Has abstractyes

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