The JAK2 V617F Mutation Seen in Myeloproliferative Neoplasms (MPNs) Occurs in Patients with Inflammatory Bowel Disease: Implications of a Pilot Study

Abstract

Patients with\rIBD frequently have hematologic abnormalities suggestive of JAK2 mutated MPNs,\rbut are traditionally classified as reactive processes. Haplotype 46/1 is a\rwell-characterized genetic predisposition, common to both inflammatory bowel\rdisease (IBD) and myeloproliferative neoplasms (MPN). In view of this shared\rgenetic predisposition, we measured the frequency of the JAK2V617F mutation in IBD patients with thrombocytosis or erythrocytosis, in order to\rascertain whether a higher than expected proportion of these patients may in\rfact have underlying MPNs. 1121 patients were identified with an active\rdiagnosis of Crohn’s disease or ulcerative colitis, of which 474 had either\rthrombocytosis or erythrocytosis. Patients with abnormal counts were tested for\rthe JAK2V617F mutation during routine follow-up visits. Interim analysis of first 23 patients tested was performed to\rassess whether the JAK2V617F positivity rate was statistically\rsignificant compared with known expected frequencies in a comparable control\rpopulation. Of 23 patients, 13 patients had thrombocytosis and 10 had\rerythrocytosis. Three patients with thrombocytosis (23%), and 1 patient with\rerythrocytosis (10%), tested positive for JAK2V617F, exceeding the\rexpected thresholds for statistical significance. In patients with IBD and\rthrombocytosis or erythrocytosis, a meaningful proportion may harbor an\rundiagnosed MPN, as indicated by clonal abnormalities such as JAK2V617F.\rThese findings imply the need for increased testing of these patients for\rclonal hematologic abnormalities, and importantly, if found, suggest the need\rfor therapeutic strategies with drugs, such as JAK2 inhibitors, in patients\rwith both MPN and IBD.