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Record W2908744276 · doi:10.1038/s41375-018-0351-2

TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups

2019· article· en· W2908744276 on OpenAlexaff
Detlef Haase, Kristen E. Stevenson, Donna Neuberg, Jaroslaw P. Maciejewski, Aziz Nazha, Mikkael A. Sekeres, Benjamin L. Ebert, Guillermo Garcia‐Manero, Claudia Haferlach, Torsten Haferlach, Wolfgang Kern, Seishi Ogawa, Yasunobu Nagata, Kenichi Yoshida, Timothy A. Graubert, Matthew J. Walter, Alan F. List, Rami S. Komrokji, Eric Padron, David A. Sallman, Elli Papaemmanuil, Peter J. Campbell, Michael R. Savona, Adam C. Seegmiller, Lionel Adès, Pierre Fenaux, Lee‐Yung Shih, David Bowen, Michael J. Groves, Sudhir Tauro, Michaëla Fontenay, Olivier Kosmider, Michal Bar‐Natan, David P. Steensma, Richard M. Stone, Michael Heuser, Felicitas Thol, Mario Cazzola, Luca Malcovati, Aly Karsan, Christina Ganster, Eva Hellström‐Lindberg, Jacqueline Boultwood, Andrea Pellagatti, Valeria Santini, Lynn Quek, Paresh Vyas, Heinz Tüchler, Peter L. Greenberg, Rafael Bejar

Bibliographic record

VenueLeukemia · 2019
Typearticle
Languageen
FieldMedicine
TopicAcute Myeloid Leukemia Research
Canadian institutionsUniversity of British Columbia
FundersMedical Research CouncilNational Institute of Diabetes and Digestive and Kidney DiseasesBlood Cancer UKDeutsche ForschungsgemeinschaftNational Cancer InstituteWashington University in St. LouisVanderbilt UniversityNational Institute for Health and Care ResearchAssociazione Italiana per la Ricerca sul CancroCelgene
KeywordsMyelodysplastic syndromesInternational Prognostic Scoring SystemInternal medicineMonosomyKaryotypeBiologyOncologyChromosome 7 (human)GeneticsMedicineChromosomeBone marrowGene

Abstract

fetched live from OpenAlex

Risk stratification is critical in the care of patients with myelodysplastic syndromes (MDS). Approximately 10% have a complex karyotype (CK), defined as more than two cytogenetic abnormalities, which is a highly adverse prognostic marker. However, CK-MDS can carry a wide range of chromosomal abnormalities and somatic mutations. To refine risk stratification of CK-MDS patients, we examined data from 359 CK-MDS patients shared by the International Working Group for MDS. Mutations were underrepresented with the exception of TP53 mutations, identified in 55% of patients. TP53 mutated patients had even fewer co-mutated genes but were enriched for the del(5q) chromosomal abnormality (p < 0.005), monosomal karyotype (p < 0.001), and high complexity, defined as more than 4 cytogenetic abnormalities (p < 0.001). Monosomal karyotype, high complexity, and TP53 mutation were individually associated with shorter overall survival, but monosomal status was not significant in a multivariable model. Multivariable survival modeling identified severe anemia (hemoglobin < 8.0 g/dL), NRAS mutation, SF3B1 mutation, TP53 mutation, elevated blast percentage (>10%), abnormal 3q, abnormal 9, and monosomy 7 as having the greatest survival risk. The poor risk associated with CK-MDS is driven by its association with prognostically adverse TP53 mutations and can be refined by considering clinical and karyotype features.

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)0.000
metaresearch head score (Gemma)0.002
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 score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.000
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 head0.018
GPT teacher head0.275
Teacher spread0.258 · 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

Citations259
Published2019
Admission routes1
Has abstractyes

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