JAK2 pathogenic variants in ischemic stroke: low prevalence and pre-screening model

Area of Science:

• Hematology
• Neurology
• Genetics

Background:

• The Janus kinase 2 (JAK2) V617F mutation is associated with myeloproliferative neoplasms.
• Its role in ischemic stroke (IS) pathogenesis and prevalence in specific cohorts remains under investigation.

Purpose of the Study:

• To determine the prevalence and clinical characteristics of JAK2 V617F mutation carriers within the CNSR-III ischemic stroke cohort.
• To develop a predictive model for identifying individuals at high risk for carrying the JAK2 V617F mutation.

Main Methods:

• Retrospective analysis of targeted sequencing data from the CNSR-III cohort to identify JAK2 pathogenic variants.
• Logistic regression analysis to compare clinical and laboratory features between JAK2 V617F mutation carriers and non-carriers.
• Development and internal validation of a JAK2 V617F screening score.

Main Results:

• The JAK2 V617F mutation was identified in 0.4% (46/10428) of the cohort.
• Carriers exhibited significantly worse functional outcomes post-stroke (adjusted OR 2.74).
• Predictors included elevated platelet count and hemoglobin, with decreased prevalence of traditional stroke risk factors (hypertension, smoking, obesity).
• The JAK2 V617F screening score demonstrated high accuracy (AUC 0.98, sensitivity 85%, specificity 94%) in predicting mutation status.

Conclusions:

• JAK2 V617F mutation represents a distinct, actionable subtype of ischemic stroke, despite its low prevalence.
• The developed screening score facilitates a precision medicine approach, potentially reducing the need for broad genetic testing in stroke patients.