IP: Dres. Andrés Celestino García Montero y Luis Escribano Mora

Resumen del proyecto: Systemic Mastocytosis (SM) is a rare disease which makes difficult to obtain a large number of patients. SM has heterogeneous clinical appearance, from indolent (ISM) forms with normal live expectation to very aggressive, life-threatening, disease (ASM). Despite of this, D816V activating c-kit mutation is present in the majority of SM patients independently of their severity. Thus, secondary genetic alterations are thought to be cause of the disease progression to the most aggressive cases.
Objective: to identify genetic alterations, secondary to D816V mutation, within the exome of SM patients who have progressed from indolent to aggressive forms of the disease, and to know the amount of infiltration these mutation could have in the hematopoiesis of SM patients with different forms of SM, to establish their importance in the severity and progression of the disease.
Patients will be diagnosed and controlled by the Spanish network on mastocytosis (REMA). All of them will give their approval, by signing an specific (inform) consent, to participate in this project which include whole exome sequencing.
Methods: 1) Immunophenotypic characterization of bone marrow (BM) cell populations by flow cytometry. 2) Purification of BM cell subsets (including mast cells) by FACSAria sorter. 3) Molecular analysis of c-KIT mutations. 4) Whole exome sequencing, using NGS methods, of DNA samples from ten patients representatives of those MSA patients who progress from indolent forms. Analysis of the correlation between sequencing, immunophenotypic and molecular data, along with the associated clinical and environmental features will allow us identify those mutations which could improve the diagnostic and prognostic criteria to predict a potential disease progression.

Entidad financiadora: Instituto de Salud Carlos III y Fundación Ramón Areces