Splicing Factor Pathway Is Rarely Mutated in Myeloid Blast Phase of PV with Dysmyelopoiesis and Ring Sideroblast
Notice bibliographique
Résumé
Abstract Introduction: BP of PV presents with dyserythropoiesis, including ring sideroblasts, and bilineage dysplasia in most cases. Clonal evolution or acquisition of new cytogenetic clone(s) plays a critical role in progression to BP of PV. SF3B1 mutation is associated with 75% of MDS with ring sideroblasts (RS). We hypothesized that an increase in ring sideroblast counts is an early event in the BP evolution. We postulate that genomic lesions other than in splicing factors genes are implicated in RS development in PV during BP evolution. Methods: We identified all cases in the last 14 years (2004 - 2018) with a diagnosis of PV in the MDACC files. We collected demographic, clinical, morphological, cytogenetic, and NGS information from 61 patients who developed BP progression from PV. We did an assessment and scoring of all bone marrow (BM) samples available at BP evolution. Results: A total of 61/477 (13%) patients with diagnosis of BP of PV were identified. Median age at BP diagnosis was 67 yrs. (32-82). This included 34 (56%) men and 27 (44%) women. At BP presentation, median BM blast percentage was 28%; 51 (84%) patients had BM dysplasia; 35 patients (69%) with dyserythropoiesis, 22 (43%) cases showed bilineage dysplasia. At BP, 43 pts had complex CG, 9 were were normal karyotype, 3 had double and 5 had single abnormalities. Prussian blue stain for Iron evaluation was available in 54 patients (89%); 24 patients (44%) had 0% RS; 19 patients (35%) had 1-14% RS; and 11 pts (20%) had >15% RS. Mutation analysis for splicing factor was performed on 13 patients. Of these, 2 patients with >15% RS had SRSF2 mutation and 1 patient with 6% RS had SF3B1 mutation. The other patients were wild type for SF3B1, SRSF2, U2AF1 (5 patients: >15% RS, 2 patients: 1-14% RS and 3 patients: 0% RS). Twenty-four (39%) patients had BM available before the BP diagnosis; median time between first BM at MDACC and BP BM diagnosis was 35 months (range, 1-135). At Baseline BM assessment, median BM blast was 3%; 13 (54%) patients had BM dysplasia. Prussian blue stain for Iron evaluation was available in 13 pts (55%): 10 pts (77%) had 0% RS and 3 pts (23%) had 1, 3, and 60% RS, respectively. To evaluate the level of RS during disease evolution we identified 10/26 pts who had at least 1 BM sample available between the first BM and the BP. 5/10 pts were in spent phase with increased blast, multilineage dysplasia and complex CG (RS: 6%, 25%, 0%, 1% and 50%) median time between samples 5 months. 4/10 pts had 1-4% blast, isolated dyserythropoiesis and normal diploid CG (RS: 12%, 5%, 2% and 0%). The median time between samples was 56 months. The last pt. had 0% blast, no dysplasia, del(20q) on CG and no RS. Pt. developed BP of PV 41 months after this follow up sample. Ten pts with PV chronic phase and were used as control group, median follow up of 14,5 yr. None of the patients had RS at baseline or at last follow up BM. Median time between samples 6 yrs. RS increase during PV evolution were statistically significant more frequent in pts who develop BP than in pts who remain in chronic phase of PV (7/10 vs. 0/10. P=0.003) Conclusion: Splicing factor gene mutation is infrequent in BP of PV despite the presence of dyserythropoiesis and frequent RS in 55% of patients. When present , RS may identify disease evolution and correlate with the disease phase of PV before BP. Dyserythropoiesis and the acquisition of RS is an early event BP of PV that precede other markers of disease progression like CG. 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 | 0,001 | 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 ».