Insights into Disease Evolution of Transformed Follicular Lymphoma Derived from Cytogenetics.
Notice bibliographique
Résumé
Abstract Background: Follicular lymphoma (FL) is an indolent lymphoma with a median survival of 8 years. Transformation to diffuse large B cell lymphoma (DLBCL) is a major cause of mortality. The critical events leading to transformation are still unknown. Studies looking at the clonal cytogenetic evolution of FL have implicated −6q, +7, +12, −17p, +der(18), +X and abnormalities in chromosomes 1 or 8 as poor prognostic factors. Methods: We investigated the effect of these abnormalities and the number of alterations per tumor (NAPT) on the risk of developing transformed lymphoma (TLy) in a cohort of FL patients treated at the British Columbia Cancer Agency (BCCA) from 1983 to 2005. Karyotypes were determined on all samples by classic G banding technique. NAPT and the presence of the previously mentioned abnormalities were determined. TLy was defined as a DLBCL or Burkitt-like or composite histology (focal DLBCL with residual FL) on repeat biopsy or the presence of one of the following clinical features: rapid discordant nodal growth, sudden rise in LDH (≥2x baseline), unusual extranodal involvement or hypercalcemia. 279 FL biopsies had available karyotypes and clinical information required for this analysis. Results: With a median follow up time of 9.5 years, 54 patients (19%) developed TLy. The mean NAPT in the initial biopsy specimen was similar whether or not TLy developed (5.3 vs 5.0). The mean NAPT in patients who developed TLy early (≤2 years) was not greater than in those who developed TLy late (> 2 years) (4.8 vs 5.2). The incidence of specific cytogenetic changes was comparable to what is reported in the literature: +X (24%), 6q- (22%), +7 (15%), +12 (10%), −17p (9%), der (18) (24%) and abnormalities in chromosomes 1 (35%) or 8 (5%). These changes did not appear to influence the risk of developing TLy nor were they more prevalent in those who developed TLy. In 12 cases where the initial and TLy karyotypes could be compared, two patterns of cytogenetic evolution emerged. In 4 cases, the initial karyotype was clearly present in the TLy karyotype, including additional secondary cytogenetic abnormalities. In the remaining 8 cases, karyotypes of the TLy lacked many of the cytogenetic abnormalities that were present in the initial biopsy, except the t(14;18) or variant. Three out of the 8 cases had a lower NAPT in the TLy. Overall, there was no correlation between the NAPT of the initial and TLy biopsies (r= −0.38 p=0.3). Amongst the 12 paired specimens, the incidence of MYC breakpoints (8q24) and P53 deletions (17p13) were greater in the TLy karyotype (25% vs 0% and 16% vs 0%, respectively). Conclusions: The karyotype in FL at diagnosis does not influence the risk of transformation and cannot be used to predict which patients will transform early. Furthermore, there is no correlation between the NAPT in the karyotypes of the paired specimens (FL→DLBCL) even though the involvement of MYC and P53 is more prevalent in the TLy karyotypes. We hypothesize that transformation is a random event that can occur in FL cells that are less clonally evolved than those represented in the initial biopsy, analogous to a “FL stem cell”. Alternatively, the initial biopsy may not have captured the particular clone that eventually resulted in transformation, favoring subclone selection rather than clonal evolution. Newer technologies that study the genome and proteome in more detail, including the effect of the microenvironment may improve our understanding of the critical events leading to FL transformation.
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 | 0,001 | 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) | 0,001 | 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 ».