Lymphomas with Concurrent T(14;18) and 8q24 Translocations Are Under- Reported and Clinical Outcome Depends on the MYC Partner
Notice bibliographique
Résumé
Abstract Background : Lymphomas with concurrent t(14;18) and 8q24 translocations (BCL2+/MYC+) are associated with a poor overall survival (OS). Recently, Savage et al. (Ann Oncol 19: 4, 2008, a186) reported that 4% (6/163) of patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) have BCL2+/MYC+ rearrangements and have a variable clinical outcome. We identified the clinical and cytogenetic characteristics of a larger cohort of patients with BCL2+/MYC+ rearrangements to determine correlations with outcome. Methods : Cases of non-Hodgkin lymphoma (NHL) with concurrent 18q21 and 8q24 breakpoints were identified by karyotype and/or fluorescence in-situ hybridization (FISH) analysis. Histological diagnoses were determined according to the World Health Organization. All MYC rearrangements were confirmed by FISH using a commercial MYC break-apart probe. OS was calculated from the MYC+ biopsy date to last follow up date or death. Results : 55 of 1480 NHL samples (4%) were identified and confirmed to have BCL2+/MYC+ rearrangements. The histological diagnoses were follicular lymphoma (FL)(1), DLBCL(17) and high-grade B cell lymphoma unclassifiable (HGBCL) (37). The HGBCL included cases that were considered intermediate between DLBCL and Burkitt lymphoma (BL), Tdt+ lymphoblastic lymphoma (LBL) and surface immunoglobulin (IG)+ acute lymphoblastic leukemia (sIG+ ALL). All HGBCL cases with available Bcl-2 protein staining were positive in contrast to 5/14 DLBCL cases that were Bcl-2 protein negative despite having t(14;18). By karyotype, 31/55 had MYC translocations involving the IG loci (11 t(8;14), 11 t(8;22), 3 t(2;8) and 6 complex t(8,14,18)). The remaining MYC rearrangements involved different chromosome partners, the most common being t(8;9) (q24;p13) (12/31). The other MYC partners included 1p36, 3p25, 3q27, 4p13, 5q13, 12p11 and 13q31. There was a high correlation between the MYC partner and the resulting histology. 28/31 of the IG/MYC translocations were associated with HGBCL. 14/17 of DLBCL cases had non-IG/MYC translocations and those with IG/MYC translocations were either Bcl-2 protein-negative (2) or had a complex t(8;14;18)(1). HGBCL histology, Bcl-2 protein expression and the presence of an IG/MYC partner all correlated with a poor outcome. HGBCL was associated with a median OS of 3 months compared to 3 y for DLBCL (p<0.0001). In contrast to the DLBCL patients, the HGBCL patients were older (median age 62 y vs 54 y), more often developed transformation from antecedent indolent lymphoma (44% vs 30%) and were less likely to complete anthracycline-based chemotherapy (76% vs 94%). Bcl-2 protein-negative biopsies were associated with median OS of 5.7 years vs 5 months for Bcl-2 protein+ cases (p = 0.05). An IG/MYC partner correlated with a median OS of 3 months compared to 7 months for non-IG/MYC partner (p=0.02). Thus, a favorable outcome was associated with DLBCL morphology, a non-IG/MYC rearrangement and Bcl-2 protein-negative biopsy. IG/MYC+ and Bcl-2 protein+ biopsies were associated with HGBCL and a median OS of < 4 months (p = 0.02). Conclusion : NHL with BCL2+/MYC+ rearrangements are under-recognized due to lack of routine karyotyping or FISH analysis of all high-grade lymphomas. Comprehensive analysis of BCL2 and MYC status should be performed on all HGBCL in the new WHO (2008) classification. The presence of an IG-related MYC partner correlates with a poor prognosis. The favorable survival associated with the few Bcl-2 protein-negative cases suggests that the anti-apoptotic effect of Bcl-2 protein explains the negative impact on prognosis when NHL have concurrent t(14;18) and MYC translocations. Thus, Bcl-2 targeted therapy should be ideally suited for the more frequent Bcl-2 protein+ cases.
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 | 0,001 | 0,002 |
| 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 | 0,001 |
| Communication savante | 0,001 | 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 ».