Below post translated from a Spanish article in diariomedico.com.
English abstract available in PubMed.
A research team of Laboratory 11 of the Cancer Research Center of Salamanca (CIC) has identified the gene expression profile (GEP) of systemic mastocytosis, explained Andrés García Montero, one of the coordinators of this research group led by Salamanca's Alberto Orfao. The researchers have identified the GEP for both the aggressive and indolent forms.
“By comparing samples of diseased and normal mast cells, we have successfully identified the GEP associated with systemic mastocytosis. Overall, 758 transcripts were significantly deregulated in patients with SM, with a common GEP of 398 genes for all subvariants of SM analyzed. These 398 genes are mainly associated with inflammatory immune responses showing overexpression of interferon-induced genes. These genes are involved in the response to virus and molecule inhibitors of the complement pathway and show increased expression of genes involved in lipid metabolism and protein” stressed Garcia Montero
In addition, Aggressive SM showed deregulation of apoptosis and cell cycle-related genes, whereas patients with indolent SM displayed increased expression of adhesion-related molecules.
As for possible future applications, the research group's goal for the short to medium term is to identify molecules that can be used for the diagnosis or monitoring of the disease through minimally invasive samples such as peripheral blood. Their mid to long term goals are to identify molecules or molecular pathways in the most aggressive forms that allow the design or selection of specific drugs to treat these patients.
This work is the result of a collaboration of nearly 20 years, in the context of the Spanish Network of Mastocytosis (REMA), the research group led by Alberto Orfao at the Center for Cancer Research and Luis Escribano's group in the Mastocytosis Unit of Castilla-La Mancha (Hospital Virgen del Valle, Toledo). It is an important part of the doctoral thesis of Cristina Teodosio and has been supported by the Instituto de Salud Carlos III in Madrid, the Ministry of Health of the Government of Castile and Leon, and the geriatric Foundation of Castilla-La Mancha with projects directed by Andrés García Montero, Luis Alberto Orfao and Escribano.
This research stems from the real need to find specific molecular markers that can predict well in advance which patients with indolent forms of mastocytosis would progress to the aggressive forms, as well as to identify what molecular pathways are differentially activated in both types of patients. This will allow us to target molecules that can be used for designing new therapeutic strategies.
To achieve this we studied the gene expression profile (GEP) of purified mast cells (with purities greater than 95-98 percent) of bone marrow samples.
The great difficulty involved in this work was precisely to obtain the biological material, because the mast cells do not spend much time in the bone marrow of healthy individuals or patients with indolent forms. (Mast Cells in bone marrow are usually very rare, typically less than 0.01 per cent of the bone marrow cells).
Even in aggressive forms it is rare that the percentage exceeds 1-3 percent. For this reason, the selection of patients and obtaining the biological material (RNA purified mast cells) took over six years of work.