JAK2 617V>F Mutation Correlates with Arterial Thrombosis in Essential Thrombocythemia.
Notice bibliographique
Résumé
Abstract Background: Philadelphia chromosome negative chronic myeloproliferative disorders (CMPD) are a group of hematopoietic stem cell disorders associated with elevated blood counts, abnormal bone marrow morphology, and often with coagulopathy. The JAK2 617V>F mutation is reported to be present in approximately half of the CMPD classified as essential thrombocythemia (ET). The mutation is currently used in diagnosis. Its relation to prognosis is unclear. Aim: The goal of this study was to determine the prognostic relevance of JAK2 617V>F mutational status in ET patients. Methods: A 12-year retrospective review of laboratory and medical records identified 255 cases of ET. The diagnosis was based on PVSG or WHO criteria. Peripheral blood, bone marrow, cytogenetics, and other laboratory findings at the time of diagnosis were catalogued. Clinical complications before and after diagnosis were documented. For cases where JAK2 617V>F status was unknown, we used InvivoScribe RFLP kit assay utilizing polyacrylamide gel electrophoresis analysis on archived bone marrow or peripheral blood samples (5% analytical sensitivity). The associations were calculated as odds ratio (OR) with 95% confidence interval (CI). Differences in continuous variables were tested using Student’s t-test and Mann-Whitney U test. Chi-square test and Fisher’s Exact test were used to compare differences in proportions. A difference was considered significant if P <0.05. Statistical analysis was performed using SPSS Version 12.0 software. Results: Complete laboratory and clinical data were available for 227 cases of ET (male:female = 0.6; mean age, 65.9 years; mean follow up, 63.7 ± 2.5 months). 125 (55.1%) patients were heterozygous and 6 (2.6%) were homozygous positive for theJAK2 617V>F mutation and 96 (42.2%) were negative. There was no significant difference in sex, age of onset survival, karyotype, or treatment rate (with hydroxyurea or anagrelide) between JAK2 617V>F positive and negative groups. The presence of mutation at the time of diagnosis correlated with higher hemoglobin (141.8 ± 1.7 vs. 128.0 ± 2.3 g/L, P = <0.001), WBC count (10.8 ± 0.4 vs. 9.6 ± 0.5 *109/L, P = <0.05), neutrophilia (7.8 ± 0.4 vs. 6.3 ± 0.3 *109/L, P = <0.02) and lower platelets (856 ± 27 vs. 954 ± 42 *109/L, P = <0.02). Standard risk factors (age ≥60 and/or previous thrombosis) showed association with thrombotic events in both groups (P = <0.04). Mutation positive patients displayed 2.4 fold greater risk of arterial thrombosis (95% CI 1.2-4.6). This risk was 3.3 fold greater before ET diagnosis (95% CI 1.4-7.9), but not significant afterwards. Venous thrombosis and bleeding were not different between groups and did not correlate with the leukocyte count. Mutation status did not predict transformation to myelofibrosis or acute leukemia. Conclusion: Our data supports the reported incidence of JAK2 617V>F mutation in ET (58%). Presence of the JAK2 617V>F mutation in ET patients does not predict survival, gender, age of onset, karyotype, risk of venous thrombosis, or bleeding. The mutation does correlate with a higher risk of arterial thrombosis in our study population. This risk appears to be highest before diagnosis of ET and equalizes after diagnosis between mutation positive and negative patients, possibly reflecting better response to therapy in the former group.
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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 | 0,002 |
| 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 | 0,000 |
| 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 ».