Enhanced Risk for Specific Somatic Myeloproliferative Neoplastic Mutations in Patients with Stroke.

Background: Somatic mutations of Janus kinase 2 (JAK2V617F), calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL) are the major clonal molecules that drive the pathogenesis of myeloproliferative neoplasms (MPN). It is well recognized that MPN patients carry an excessive risk of thrombohemorrhagic complications. However, little is known about the prevalence of these clonal markers in patients with cerebral vascular disease.

Methods: To address this issue, 153 consecutive stroke patients in Taiwan were enrolled in the study. Allele-specific PCR (AS-PCR), real-time AS-PCR, and Illumina paired-end sequencing were employed to detect the presence of MPL, JAK2V617F, and CALR exon 9 mutations, respectively.

Results: JAK2V617F mutation was detectable in 13 samples (8.5%), but the allele burdens (AB) were greater than 1% in only six (3.9%) of them. Compared to JAK2-unmutated patients, those with JAK2V617F AB > 1% had significantly higher white blood count (p = 0.01), although four of the six did not exhibit MPN phenotypes. Two patients had a heterozygous CALR exon9 mutation locating outside the coding region and did not alter the amino acid sequence of this protein. On the other hand, there were no patients carrying the MPL mutations. Using patient age, baseline hemogram, and stroke-relevant risk factors, we developed a predictive model that could successfully identify stroke patients at risk of carrying clonal JAK2V617F mutation.

Conclusion: The prevalence of JAK2V617F mutation in stroke patients was higher than that seen in general population. Based on our newly developed probability stratification model, genotyping of JAK2V617F mutation in selected patients with stroke might be warranted.