Chromosomal Abnormalities in Bone Marrow Lymphocytes of MM Patients
Notice bibliographique
Résumé
Abstract Abstract 4045 Multiple Myeloma (MM) is characterized by accumulations of chromosomal abnormalities throughout the course of disease. Recurrent IgH translocations such as t(4;14) or deletion (del)13 occur during early stages of disease or perhaps as originating events. Other abnormalities appear to be acquired late in the disease process, after development of frank MM, including p53 deletion (Ch17) and amplification of CKS-1B (Ch1). We have previously identified drug resistant clonotypic B lymphocytes in MM that have malignant characteristics and can xenograft MM to immunodeficient mice. Using an automatic scanning system we scanned bone marrow (BM) cytospin slides stained with May-Grünwald Giemsa to identify lymphocytes and to determine whether or not they share the same chromosomal abnormalities that are found in autologous plasma cells (PC). For 200 MM patients, we performed interphase FISH using commercial probes, to detect deletion of chromosome 13, any translocations in 14q32, t(4;14)(p16;q32),t(11;14)(q13;q32), deletion of p53 and a custom probe to detect amplification of CKS-1B. For patients harboring a given chromosomal abnormality in their PC, we found the identical abnormalities in BM lymphocytes for 35% of patients having del13, 30% having t(4;14) and 23% having t(11;14). Likewise we detected amplification of locus 4p16, 11q13, 14q32, trisomy 1 and trisomy 17 in 45%, 15%, 30%, 37.5% and 44% respectively in the lymphocytes of patients demonstrating those same abnormalities in the PC. In a more limited series of experiments using immuno-FISH, we observed that BM lymphocytes with chromosomal abnormalities expressed CD20. In contrast, amplification of CKS-1B or p53deletion were undetectable in lymphocytes from patients having these abnormalities in their PC. We are currently analyzing the impact of abnormalities present in BM lymphocytes with regards to the clinical parameters and survival. An update of these results will be given at the meeting. Given the compelling evidence that B cells comprise a clinically important compartment of the MM clone, this work suggests that fundamental genetic events shared by all compartments of the MM clone include recurrent IgH translocations and Ch13 deletions. However, further clonal expansion occurring during disease progression and after relapse may be restricted to the PC population, characterized by acquisition of p53 deletions and CSK1B amplification. Furthermore in overt MM, clonal expansion may simultaneously occur on at least two levels, firstly that of the B cells which persistently give rise to PC, and secondly that of PC themselves as they continue clonal expansion in the absence of contributions from the B cells. Abnormalities such as del13 or IgH translocations characterize early events in the disease while p53del or amplification of CKS-1B may occur as progression events restricted to PC. Disclosures: No relevant conflicts of interest to declare.
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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 | 0,000 |
| 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) | 0,003 | 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 ».