Abstract 3897: Ribosomal translational regulation is a potential mechanism for leukemia-related thrombo-embolic event in childhood acute lymphoblastic leukemia
Notice bibliographique
Résumé
Abstract Introduction: Thrombo-embolic event (TE) is a frequent complication of childhood acute lymphoblastic leukemia (cALL) and is associated with reduced survival. Overexpression of podoplanin or coagulome genes and coagulation pathway activation have been identified in cancer-induced TE but the role of leukemia environment in TE occurrence has not been fully elucidated in ALL. We assessed whether leukemia gene expression (GE) signature at diagnosis was associated with TE development in cALL. Methods: We included children aged 0-18 years old (y.o.), from two hospitals, with newly diagnosed ALL and available RNA sequencing data from bone marrow at diagnosis. The primary outcome was the occurrence of grade ≥2 TE during ALL therapy using the Ponte Di Legno Working Group classification. TEs were classified as early (ET) if they occurred within 6 weeks from treatment start, or late (LT) otherwise. We compared differential gene expression (DE) in children with and without TE, adjusted for age (<10 or ≥10 y.o.) and ALL type (T or B-ALL). A secondary analysis stratified children between ET, LT and no TE. Gene set enrichment analysis (GSEA) was performed on KEGG and gene ontology (GO) databases. DE with absolute fold change ≥2 and p-values <0.05 were considered significant. Results: We included 80 patients (median age: 5 years [interquartile range, IQR: 3-11 years], 53% male, 83% precursor B-cell ALL) of whom 19 (23.8%) developed a TE (7 ET and 12 LT) at a median of 76 days (IQR: 31-133 days) following cancer diagnosis. Patients with TE were more likely to be ≥10 y.o., while other demographic and clinical characteristics were similar. No genes from the coagulome, podoplanin or Hallmark coagulation pathways were differentially expressed in children with and without TE. The KEGG Ribosome pathway was the most upregulated pathway in the group with TE (normalized enrichment score (NES) = 2.35, adjusted p-value= 0.012) and ET (NES = 2.63, adjusted p-value < 0.001). LT was not significantly associated with ribosome pathway dysregulation. Interestingly, prior reports identified functional enrichment in ribosomal pathway as a biomarker for venous TE. A heatmap classification for ribosomal genes revealed 3 distinct signatures: ribosomal downregulation, moderate and high ribosomal activation. High ribosomal activation profile was seen in 6/7 ET and 9/12 LT, corresponding to a positive and negative predictive value of 0.55 and 0.92 for TE, respectively. Conclusion: TEs in cALL were not associated with dysregulation in coagulation pathways or podoplanin gene at the RNA level. However, ribosomal translational pathway was highly upregulated in the group with thrombosis, particularly with ET. Dysregulation of posttranscriptional machinery might explain the pro-thrombotic effect of leukemia environment in cALL and warrants further investigation including proteomic exploration. Citation Format: Marie-Claude Pelland-Marcotte, Meredith Michelle Rémy, Yan Ma, Jessica Liu, Camille Jimenez-Cortes, Thomas Sontag, Maxime Caron, Pascal Saint-Onge, Sylvie Langlois, Charles Joly-Beauparlant, Daniel Sinnett, Arnaud Droit, Thai Hoa Tran, Raoul Santiago. Ribosomal translational regulation is a potential mechanism for leukemia-related thrombo-embolic event in childhood acute lymphoblastic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3897.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».