Role of the JAK2 mutation in the diagnosis of chronic myeloproliferative disorders in splanchnic vein thrombosis

Authors

  • Massimo Primignani,

    1. Gastroenterology Unit and Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialties, University of Milan and IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy
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    • M. P., G. B., and P. M. M. designed the study and wrote the first draft of the manuscript. G. B. performed JAK2 genotype and clonality assays. U. G. and G. B. performed the bone marrows biopsies. F. F., R. R., A. D., and P, B, collected and analyzed clinical and laboratory data.

  • Giovanni Barosi,

    1. Clinical Epidemiology Unit, IRCCS Policlinico S. Matteo, Pavia, Italy
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    • M. P., G. B., and P. M. M. designed the study and wrote the first draft of the manuscript. G. B. performed JAK2 genotype and clonality assays. U. G. and G. B. performed the bone marrows biopsies. F. F., R. R., A. D., and P, B, collected and analyzed clinical and laboratory data.

  • Gaetano Bergamaschi,

    1. Clinical Medicine Unit, IRCCS Policlinico S. Matteo, Pavia, Italy
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    • M. P., G. B., and P. M. M. designed the study and wrote the first draft of the manuscript. G. B. performed JAK2 genotype and clonality assays. U. G. and G. B. performed the bone marrows biopsies. F. F., R. R., A. D., and P, B, collected and analyzed clinical and laboratory data.

  • Umberto Gianelli,

    1. Pathology Unit and Department of Medicine, Surgery and Dentistry, San Paolo Hospital, University of Milan, Italy
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    • M. P., G. B., and P. M. M. designed the study and wrote the first draft of the manuscript. G. B. performed JAK2 genotype and clonality assays. U. G. and G. B. performed the bone marrows biopsies. F. F., R. R., A. D., and P, B, collected and analyzed clinical and laboratory data.

  • Federica Fabris,

    1. Gastroenterology Unit and Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialties, University of Milan and IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy
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    • M. P., G. B., and P. M. M. designed the study and wrote the first draft of the manuscript. G. B. performed JAK2 genotype and clonality assays. U. G. and G. B. performed the bone marrows biopsies. F. F., R. R., A. D., and P, B, collected and analyzed clinical and laboratory data.

  • Raffaella Reati,

    1. Gastroenterology Unit and Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialties, University of Milan and IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy
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    • M. P., G. B., and P. M. M. designed the study and wrote the first draft of the manuscript. G. B. performed JAK2 genotype and clonality assays. U. G. and G. B. performed the bone marrows biopsies. F. F., R. R., A. D., and P, B, collected and analyzed clinical and laboratory data.

  • Alessandra Dell'Era,

    1. Gastroenterology Unit and Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialties, University of Milan and IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy
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    • M. P., G. B., and P. M. M. designed the study and wrote the first draft of the manuscript. G. B. performed JAK2 genotype and clonality assays. U. G. and G. B. performed the bone marrows biopsies. F. F., R. R., A. D., and P, B, collected and analyzed clinical and laboratory data.

  • Paolo Bucciarelli,

    1. Gastroenterology Unit and Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialties, University of Milan and IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy
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    • M. P., G. B., and P. M. M. designed the study and wrote the first draft of the manuscript. G. B. performed JAK2 genotype and clonality assays. U. G. and G. B. performed the bone marrows biopsies. F. F., R. R., A. D., and P, B, collected and analyzed clinical and laboratory data.

  • Pier Mannuccio Mannucci

    Corresponding author
    1. Gastroenterology Unit and Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialties, University of Milan and IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy
    • Via Pace 9, 20122 Milano, Italy
    Search for more papers by this author
    • M. P., G. B., and P. M. M. designed the study and wrote the first draft of the manuscript. G. B. performed JAK2 genotype and clonality assays. U. G. and G. B. performed the bone marrows biopsies. F. F., R. R., A. D., and P, B, collected and analyzed clinical and laboratory data.

    • fax: (39) 02-50320723


  • See Editorial on Page 1391

  • Potential conflict of interest: Nothing to report.

Abstract

The diagnosis of an underlying chronic myeloproliferative disorder (CMPD) is often problematic in patients with primary extrahepatic portal vein obstruction (EHPVO) or Budd-Chiari syndrome (BCS); indeed, conventional clinical and hematological parameters usually yield insufficient information. To assess the diagnostic contribution of the gain-of-function mutation V617F of the JAK2 gene, 93 patients with EHPVO or BCS were investigated. JAK2 V617F was identified in 35.6% of 73 patients with EHPVO and in 40% of 20 patients with BCS. Taking the JAK2 mutation as a test with the highest positive predictive value for the diagnosis of CMPD, conventional clinical-hematological parameters had a sensitivity for CMPD lower than 48%. Bone marrow (BM) histology provided a diagnosis of CMPD in 41/74 (55.4%) patients, with a sensitivity of 93.5%. Clonality of hematopoiesis as assessed by granulocyte X-chromosome inactivation was present in 65.1% of 43 informative female patients, with a sensitivity of 86.6%. By resolving the sensitivity bias of the JAK2 mutation with the results of BM histology and clonality assay, CMPD was diagnosed in 53% of patients with EHPVO or BCS. In conclusion, CMPD is the major cause of primary EHPVO or BCS. JAK2 V617F is a very reliable and noninvasive molecular marker for CMPD and should be used as a first test for diagnosis. (HEPATOLOGY 2006;44:1528–1534.)

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