[Current concepts and treatment advances in systemic mastocytosis].
OBJECTIVE
Mast cell disorders are defined by an abnormal accumulation of tissue mast cells in one or more organ systems. Clinical symptoms in mastocytosis result from mast cells derived mediators and, less frequently, from destructive infiltration of mast cells. Systemic mastocytosis is regressive among children, whereas the disease is persistent among adults. A clonal haematological non-mast cell lineage disease can be associated. The clinical course in these patients is variable ranging from asymptomatic for years to highly aggressive and rapidly devastating. Until recently, the only treatment of this incurable disease was symptomatic.


BACKGROUND
Recent advances were done in understanding the physiopathology of this myeloproliferative syndrome which results from an activating mutation of the stem cell factor receptor: C-Kit. A somatic C-Kit mutation is usually detectable in mast cells and their progenitors. Different mutations were found and the mutation D816V is the most frequent. Their specific transduction paths were also studied. Diagnosis of systemic mastocytosis does not only rest upon pathological examination but also on molecular as well as immunological and immunochemical tools.


CONCLUSIONS
Physiopathological advancements led to suggest new treatments in order to directly inhibit proliferative paths of masts cells such as tyrosine kinase inhibitors and rapamycin.
Georgin-Lavialle
S
S
Service d'hématologie adultes, CNRS-UMR 8147, centre de référence sur les mastocytoses, hôpital Necker-Enfants-Malades, université Paris-V, Paris, France.
Barete
S
S
Suarez
F
F
Lepelletier
Y
Y
Bodemer
C
C
Dubreuil
P
P
Lortholary
O
O
Hermine
O
O
D000328:Adult; D001897:Boronic Acids / Q000008:administration & dosage / Q000627:therapeutic use; D000069286:Bortezomib; D002648:Child; D005544:Forecasting; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D034721:Mastocytosis, Systemic / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D009154:Mutation; D011379:Prognosis; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011719:Pyrazines / Q000008:administration & dosage / Q000627:therapeutic use; D020123:Sirolimus / Q000008:administration & dosage / Q000627:therapeutic use; D033581:Stem Cell Transplantation; D014161:Transduction, Genetic; D014944:World Health Organization
D001897:Boronic Acids; D007166:Immunosuppressive Agents; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D019009:Proto-Oncogene Proteins c-kit; D020123:Sirolimus