IFN-γ (interferon-gamma) Genotype Predict Cytogenetic and Molecular Response to Imatinib Therapy in Chronic Myeloid Leukemia.
Notice bibliographique
Résumé
Abstract Abstract 2178 Poster Board II-155 Purpose: Interferon therapy had served as a standard therapy before introduction of imatinib into the treatment of chronic myeloid leukemia (CML) although its action mechanism is yet fully elucidated. After introduction of imatinib therapy, it provides significant therapeutic benefit to CML patients, however its response varies person-by-person. Some patient responds quickly and maintain long-term response without development of resistance, while others do not respond well or lose their response quickly thus developing resistance to imatinib. One of interesting observation is that the patients previously treated with interferon could maintain long-term complete molecular response (CMR) even after withdrawal of imatinib therapy, suggesting interferon signaling pathway seemed to be associated with favorable response to imatinib therapy. Variable response to imatinib therapy in CML can be explained by inter-individual variation of candidate genes involved in the biologic activity of CML cells such as apoptosis or angiogenesis as well as drug transport/metabolism of imatinib in addition to Interferon gamma signaling pathway. Methods: In the current study, we investigated 80 single nucleotide polymorphism (SNP) markers involved in the pathways of apoptosis (n=31; BCL2, BAX, BCL2L2, BCL6, BCL2L11, BIRC5, CASP1, CASP3, CASP7,CASP8, CASP9, CASP10, FAS, FASL, APAF1, TNFR2, PDCD1, GZMB), angiogenesis (n=7; VEGFA, VEGFR2), myeloid cell growth (n=13; FLT2, CSF3, CSF2, JAK3, IL1A, IL1B, IL1R), xenobiotic metabolism (n=13; ABCB1, ABCG2, CYP3A5, HOCT1), WT1 signaling (n=7), interferon signaling (n=4; IFNG, IFNGR1, IFNGR2) and others (n=5; GNB3, ULK3, ORM, PTK2). Discovery cohort includes 244 patients treated at the Princess Margaret Hospital, Toronto, ON, Canada. The DNAs from peripheral blood samples were genotyped with MALDI-TOF based technique (Sequenom). The results were validated internally using a Bootstrap procedure, and externally in an independent validation cohort of 187 Korean CML patients treated at the Samsung Medical Center, Seoul, Korea or Chonnam National University Hwasun Hospital, Hwasun, Korea. Results: In a single marker analysis, several genotypes were found to be correlated with complete cytogenetic response (CCR; IFNG “p-value, 0.01”, FAS “0.03”, FASL “0.006”, CASP8 “0.04”, CASP10 “0.04”), major molecular response (MMR; IFNG “0.04”, FAS “0.05”, JAK3 “0.03”), loss of response (IFNG “0.02”, BIRC5 “0.02”), treatment failure (IFNG “0.07”), or dose escalation of imatinib (IFNG “0.03”, ABCG2 “0.02”, APAF1 “0.04”, CASP2, “0.03”). Bootstrap methods showed a good correlation of each genotype with clinical outcomes. External validation was performed in an independent cohort with 187 Korean CML patients, the IFNG genotype (rs2069705) was validated that is able to predict CCR (HR, 0.46; p=3×10-5) or MMR (HR, 0.51; p=7×10-5) in CML patients. Conclusions: The current study suggested that the interferon gamma genotype seemed to predict the response to imatinib therapy, proposing potential involvement of interferon-gamma signaling pathway in the action mechanism of imatinib therapy in CML. Further detailed study on IFNG genotype and functional study of interferon gamma phenotype will help us to reach a clear conclusion on the role of IFNG gene in the action mechanism of imatinib therapy in CML. Disclosures: No relevant conflicts of interest to declare.
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 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| 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) | 0,002 | 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 ».