Am J Cancer Res 2013;3(2):159-172
Review Article
Mastocytosis: a paradigmatic example of a rare disease with complex biology
and pathology
Peter Valent
Department of Medicine I, Division of Hematology and Hemostaseology and Ludwig Boltzmann Cluster Oncology, Medical
University of Vienna, Währinger Gürtel 18-20 Vienna, Austria
Received March 1, 2013; Accepted March 19, 2013; Epub April 3, 2013; Published April 13, 2013
Abstract: Mastocytosis is a rare disease characterized by abnormal expansion and accumulation of tissue mast cells (MC) in
one or multiple organs. In most adult patients, systemic mastocytosis (SM) is diagnosed. Based on histopathological findings
and organ damage, SM is divided into indolent SM (ISM), smoldering SM (SSM), SM with an associated hematologic non-MC-
lineage disease (SM-AHNMD), aggressive SM (ASM), and MC leukemia (MCL). The clinical course and prognosis vary greatly
among these groups of patients. In all variants of SM and most patients, neoplastic cells display the KIT mutation D816V. This
suggests that additional KIT-independent molecular defects cause progression. Indeed, additional oncogenic lesions, including
RAS- and TET2 mutations, have recently been identified in advanced SM. In patients with SM-AHNMD, such additional lesions
are often detectable in the ‘AHNMD-component’ of the disease. Clinically relevant symptoms of SM result from i) malignant MC
infiltration and the subsequent organ damage seen in advanced SM and/or ii) the release of pro-inflammatory and vasoactive
mediators from MC, found in all disease-variants. Therapy of SM has to be adjusted to the individual situation in each patient. In
ISM, the aim is to control mediator release and mediator effects. In advanced SM, a major goal is to control MC expansion by
using conventional drugs or novel targeted drugs directed against mutant forms of KIT and/or other pro-oncogenic kinase-
targets. In rapidly progressing ASM, MCL and drug-resistant AHNMD, chemotherapy and subsequent stem cell transplantation
has to be considered. (AJCR0000184)
Keywords: Mastocytosis, mast cells, rare disease, KIT mutations, targeted therapy
Address correspondence to: Dr. Peter Valent, Department of Internal Medicine I, Division of Hematology & Hemostaseology and
Ludwig Boltzmann Cluster Oncology, The Medical University of Vienna, Währinger Gürtel 18-20 Vienna, Austria. Phone: + 43 1
40400 6085; Fax: + 43 1 40400 4030; E-mail: peter.valent@meduniwien.ac.at
Review Article
Mastocytosis: a paradigmatic example of a rare disease with complex biology
and pathology
Peter Valent
Department of Medicine I, Division of Hematology and Hemostaseology and Ludwig Boltzmann Cluster Oncology, Medical
University of Vienna, Währinger Gürtel 18-20 Vienna, Austria
Received March 1, 2013; Accepted March 19, 2013; Epub April 3, 2013; Published April 13, 2013
Abstract: Mastocytosis is a rare disease characterized by abnormal expansion and accumulation of tissue mast cells (MC) in
one or multiple organs. In most adult patients, systemic mastocytosis (SM) is diagnosed. Based on histopathological findings
and organ damage, SM is divided into indolent SM (ISM), smoldering SM (SSM), SM with an associated hematologic non-MC-
lineage disease (SM-AHNMD), aggressive SM (ASM), and MC leukemia (MCL). The clinical course and prognosis vary greatly
among these groups of patients. In all variants of SM and most patients, neoplastic cells display the KIT mutation D816V. This
suggests that additional KIT-independent molecular defects cause progression. Indeed, additional oncogenic lesions, including
RAS- and TET2 mutations, have recently been identified in advanced SM. In patients with SM-AHNMD, such additional lesions
are often detectable in the ‘AHNMD-component’ of the disease. Clinically relevant symptoms of SM result from i) malignant MC
infiltration and the subsequent organ damage seen in advanced SM and/or ii) the release of pro-inflammatory and vasoactive
mediators from MC, found in all disease-variants. Therapy of SM has to be adjusted to the individual situation in each patient. In
ISM, the aim is to control mediator release and mediator effects. In advanced SM, a major goal is to control MC expansion by
using conventional drugs or novel targeted drugs directed against mutant forms of KIT and/or other pro-oncogenic kinase-
targets. In rapidly progressing ASM, MCL and drug-resistant AHNMD, chemotherapy and subsequent stem cell transplantation
has to be considered. (AJCR0000184)
Keywords: Mastocytosis, mast cells, rare disease, KIT mutations, targeted therapy
Address correspondence to: Dr. Peter Valent, Department of Internal Medicine I, Division of Hematology & Hemostaseology and
Ludwig Boltzmann Cluster Oncology, The Medical University of Vienna, Währinger Gürtel 18-20 Vienna, Austria. Phone: + 43 1
40400 6085; Fax: + 43 1 40400 4030; E-mail: peter.valent@meduniwien.ac.at
| AJCR Copyright © 2010-present, All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711, USA |
 | |  | |  | |  | |  | |  | |  | |  |
American Journal of Cancer Research
| ISSN: 2156-6976 |