Mastocytosis is a term used for a group of disorders defined by an abnormal accumulation of mast cells (MCs) in one or more organ systems. Clinical symptoms result from MC-derived mediators and/or from infiltration of MCs in the tissues. Cutaneous mastocytosis (CM) is a benign disease of the skin and often regresses spontaneously. Systemic mastocytosis (SM) is a persistent clonal disease of MCs with a variable clinical picture and a variable prognosis. Notably, the clinical course in SM ranges from asymptomatic and indolent over many years to highly aggressive with a short survival. The WHO classification discriminates four categories of SM: indolent SM (ISM), aggressive SM (ASM), SM with an associated clonal hematologic non-MC-lineage disease (SM-AHNMD), and mast cell leukemia (MCL). The genetic hallmark of SM is the somatic KIT mutation D816V. In SM-AHNMD, additional or alternative molecular defects might be detected, such as the FIP1L1/PDGFRA fusion gene in associated chronic eosinophilic leukemia (SM-CEL) or AML1/ETO in SM with acute myeloid leukaemia (AML) and t(8;21). Patients with ISM are treated with ‘mediator-targeting’ drugs, whereas patients with ASM or MCL are candidates for cytoreductive therapy. The use of ‘KIT-targeting’ tyrosine kinase (TK) inhibitors has also been suggested. Unfortunately, the D816V KIT mutation is associated with resistance against imatinib. However, several second-generation TK inhibitors, such as PKC412 (midostaurin), AMN107 (nilotinib), or BMS354825 (dasatinib) are available and reportedly inhibit growth of MCs carrying KIT D816V. These drugs might be useful for therapy of ASM or MCL in the future.


Mast Cell Systemic Mastocytosis Human Mast Cell Urticaria Pigmentosa Mast Cell Leukemia 
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© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Peter Valent
    • 1
  1. 1.Medical University of ViennaAustria

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