Published online before print December 28, 2007

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Journal of Molecular Diagnostics 2008, Vol. 10, No. 1
Copyright © 2008 American Society for Investigative Pathology & Association for Molecular Pathology
DOI: 10.2353/jmoldx.2008.070061

Systemic Mastocytosis Associated with Chronic Idiopathic Myelofibrosis

A Distinct Subtype of Systemic Mastocytosis-Associated Clonal Hematological Nonmast Cell Lineage Disorder Carrying the Activating Point Mutations KIT^D816V and JAK2^V617F

Karl Sotlar^*, Anja Bache^*, Florian Stellmacher, Burkhard Bültmann^*, Peter Valent and Hans-Peter Horny

From the Institutes of Pathology, *University of Tübingen, Tübingen, Germany; the University of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany; Klinikum Ansbach, Ansbach, Germany; and the Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria

In 20 to 30% of patients with systemic mastocytosis (SM), an associated clonal hematological nonmast cell lineage disorder (AHNMD) is diagnosed. Although SM may be considered to be closely related to the myeloproliferative disorders (MPDs), it is unknown whether JAK2^V617F+ MPD may occur as AHNMD in patients with SM. We here describe five patients with SM and co-existing chronic idiopathic myelofibrosis (SM-CIMF). In five of five patients, we detected the SM-related KIT mutation D816V, and in four of five patients, the MPD-related JAK2 mutation V617F. Surprisingly, JAK2^V617F was found not only in the AHMMD component of the disease but also in microdissected mast cells in all four JAK2^V617F-positive cases. Conversely, in two of the five patients, KIT^D816V was found not only in neoplastic mast cells but also in microdissected CD15⁺ neoplastic myeloid cells. Control experiments showed that 10 indolent SM patients without associated MPD did not carry the JAK2 mutation V617F and that 15 CIMF patients without SM did not carry the KIT mutation D816V. Altogether, these data suggest that KIT^D816V+ SM can co-exist with JAK2^V617F+ CIMF and that, in some of these SM-CIMF cases, the two mutations are present in the neoplastic cells of both disease components.