The JAK2V617F Mutation Seen in Myeloproliferative Neoplasms (MPNs) Occurs in Patients with Inflammatory Bowel Disease: Implications of a Pilot Study


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

Share and Cite:

E. Kuriakose, E. Lascu, Y. Wang, S. Gjoni, N. Cross, R. Baumann, K. Tam, E. Scherl, R. Longman and R. Silver, "The JAK2V617F Mutation Seen in Myeloproliferative Neoplasms (MPNs) Occurs in Patients with Inflammatory Bowel Disease: Implications of a Pilot Study," International Journal of Clinical Medicine, Vol. 4 No. 12A, 2013, pp. 10-15. doi: 10.4236/ijcm.2013.412A1003.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] P. M. Irving, K. J. Pasi and D. S. Rampton, “Thrombosis and Inflammatory Bowel Disease,” Clinical Gastroenterology and Hepatology, Vol. 3, No. 7, 2005, pp. 617-628.
[2] D. Silvio, C. de la Motte and C. Fiocchi, “Platelets in Inflammatory Bowel Disease: Clinical, Pathogenic, and Therapeutic Implications,” American Journal of Gastroenterology, Vol. 99, No. 5, 2004, pp. 938-945.
[3] M. Griesshammer, M. Bangerter, T. Sauer, R. Wennauer, L. Bergmann and H. Heimpel, “Aetiology and Clinical Significance of Thrombocytosis: Analysis of 732 Patients with an Elevated Platelet Count,” Journal of Internal Medicine, Vol. 245, No. 3, 1999, pp. 295-300.
[4] A. I. Schafer, “Thrombocytosis,” New England Journal of Medicine, Vol. 350, No. 12, 2004, pp. 1211-1219.
[5] A. M. Vanucchi and T. Barbui, “Thrombocytosis and Thrombosis. Hematology, Vol. 2007, No. 1, 2007, pp. 363-370.
[6] B. Anger, J. W. Janssen, H. Schrezenmeier, R. Hehlmann, H. Heimpel and C. R. Bartram, “Clonal Analysis of Chronic Myeloproliferative Disorders Using X-Linked DNA Polymorphisms,” Leukemia, Vol. 4, No. 4, 1990, pp. 258-261.
[7] Y. L. Wang, K. Vandris, A. V. Jones, N. C. Cross, P. Christos, F. Adriano and R. T. Silver, “JAK2 Mutations Are Present in All Cases of Polycythemia Vera,” Leukemia, Vol. 22, No. 6, 2008, p. 1289.
[8] J. J. Kiladjian, “The Spectrum of JAK2-Positive Myeloproliferative Neoplasms,” HEMATOLOGY American Society of Hematology Education Program, Vol. 2012, No. 1, 2012, pp. 561-566.
[9] S. Y. Kristinsson, O. Landgren, J. Samuelsson, M. Bjorkolm and L. R. Goldin, “Autoimmunity and the Risk of Myeloproliferative Neoplasms,” Haematologica, Vol. 95, No. 7, 2010, pp. 1216-1220.
[10] A. V. Jones and N. C. P. Cross, “No Association between Myeloproliferative Neoplasms and the Crohn’s Disease-Associated STAT3 Predisposition SNP rs744166,” Haematologica, Vol. 95, No. 7, 2010, pp. 1226-1227.
[11] J. C. Barrett, S. Hansoul, D. L. Nicolae, J. H. Cho, R. H. Duerr, J. D. Rioux, et al., “Genomewide Association Defines More Than 30 Distinct Susceptibility Loci for Crohn’s Disease,” Nature Genetics, Vol. 40, No. 8, 2008, pp. 955-962.
[12] K. Wang, H. Zhang, S. Kugathasan, V. Annese, J. P. Bradfield, R. K. Russell, et al., “Diverse Genome-Wide Association Studies Associate the IL12/IL23 Pathway with Crohn Disease,” The American Journal of Human Genetics, Vol. 84, No. 3, 2009, pp. 399-405.
[13] A. V. Jones, A. Chase, R. T. Silver, D. Oscier, K. Zoi, Y. L. Wang, et al., “JAK2 Haplotype Is a Major Risk Factor for the Development of Myeloproliferative Neoplasms,” Nature Genetics, Vol. 41, No. 4, 2009, pp. 446-449.
[14] D. Olcaydu, A. Harutyunyan, R. Jager, T. Berg, B. Gisslinger, I. Pabinger, et al., “A Common JAK2 Haplotype Confers Susceptibility to Myeloproliferative Neoplasms,” Nature Genetics, Vol. 41, No. 4, 2009, pp. 450-454.
[15] O. Kilpivaara, S. Mukherjee, A. M. Schram, M. Wadleigh, A. Mullally, B. L. Ebert, et al., “A Germline JAK2 SNP Is Associated with Predisposition to the Development of JAK2(V617F)-Positive Myeloproliferative Neoplasms,” Nature Genetics, Vol. 41, No. 4, 2009, pp. 455-459.
[16] S. Brand, “Crohn’s Disease: Th1, Th17 or Both? The Change of a Paradigm: New Immunological and Genetic Insights Implicate Th17 Cells in the Pathogenesis of Crohn’s Disease,” Gut, Vol. 58, No. 8, 2009, pp. 1152-1167.
[17] G. Finazzi, X. T. Gregg, T. Barbui and J. T. Prchal, “Idiopathic Erythrocytosis and Other Non-Clonal Polycythemias,” Best Practice & Research: Clinical Haematology, Vol. 19, No. 3, 2006, pp. 471-482.
[18] J. L. Spivak and R. T. Silver, “The Revised World Health Organization Diagnostic Criteria for Polycythemia Vera, Essential Thrombocytosis, and Primary Myelofibrosis: An Alternative Proposal,” Blood, Vol. 112, No. 2, 2008, pp. 231-239.
[19] R. T. Silver, W. Chow, A. Orazi, S. P. Arles and S. J. Goldsmith, “Evaluation of WHO Criteria for Diagnosis of Polycythemia Vera: A Prospective Analysis,” Blood, Vol. 122, No. 11, 2013, pp. 1881-1886.
[20] G. Bergamaschi, A. Di Sabatino, R. Albertini, S. Ardizzone, P. Biancheri, E. Bonetti, et al., “Prevalence and Pathogenesis of Anemia in Inflammatory Bowel Disease. Influence of Anti-Tumor Necrosis Factor-Alpha Treatment,” Haematologica, Vol. 95, No. 1, 2010, pp. 199-205.
[21] H. Reikvam and R. V. Tiu, “Venous Thromboembolism in Patients with Essential Thrombocythemia and Polycythemia Vera,” Leukemia, Vol. 26, No. 4, 2012, pp. 563-571.
[22] O. Karimi, J. B. Crusius, C. Coucoutsi, R. Heijmans, A. M. Sambuelli, A. S. Pena, et al., “JAK2 V617F Mutation Is Not Involved in Thromboembolism in IBD,” Inflammatory Bowel Diseases, Vol. 14, No. 11, 2008, pp. 1606-1607.
[23] S. Verstovsek, R. A. Mesa, J. Gotlib, R. S. Levy, V. Gupta, J. F. DiPersio, et al., “A Double-Blind, Placebo Controlled Trial of Ruxolitinib for Myelofibrosis,” New England Journal of Medicine, Vol. 366, No. 9, 2012, pp. 799-807.
[24] S. Verstovsek, “Therapeutic Potential of JAK2 Inhibitors,” Hematology, Vol. 2009, No. 1, 2009, pp. 636-642.
[25] W. J. Sandborn, S. Ghosh, J. Panes, I. Vranic, C. Su, S. Rousell, et al., “Tofacitinib, an oral Janus Kinase Inhibitor, in Active Ulcerative Colitis,” New England Journal of Medicine, Vol. 367, No. 7, 2012, pp. 616-624.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.