Pages Menu
TwitterRssFacebook
Categories Menu

Posted by on Jun 14, 2013 in Medical Journals |

Assessing anaphylactic risk? Consider mast cell clonality.

Head for The Masto Townhall forum to debate this paper.
This article may be copyrighted. Notice to copyright holders.
You can view the full article at the publisher here
This is a free article and no fee is due to download it.
J Allergy Clin Immunol. 2009 Mar;123(3):687-8. doi: 10.1016/j.jaci.2009.02.003.

Assessing anaphylactic risk? Consider mast cell clonality.

Metcalfe DD, Schwartz LB.

Abstract

Eosinophilic and mast cell disorders are uncommon hematologic entities, but they can carry significant morbidity and lead to devastating end-organ sequelae. In the past ten years, extensive work has led to the discovery of certain molecular abnormalities underlying a subset of these diseases. A significant minority of patients with clonal eosinophilia carry abnormal gene fusions involving PDGFRA, PDGFRB, and FGFR1. These findings have been quite significant, as those individuals with a FIP1L1-PDGFRA fusion have an exquisite susceptibility to tyrosine kinase inhibitors (TKIs), such as imatinib mesylate. Imatinib leads to a rapid remission in these patients and aborts the clinical trajectory of the disease. Unfortunately, TKIs have not been shown to be particularly active in the case of mastocytosis, although the majority of patients with mastocytosis carry a c-KIT alteration, a target of agents such as imatinib. The reason for this decreased sensitivity to TKIs is related to the resistance of the D816V variant of c-KIT, found in the majority of patients with mastocytosis. Nevertheless, investigation is ongoing to define new molecular lesions in these diseases, and potentially new targets for therapy. Clinical trials are also investigating other novel small molecules that may have efficacy against targets currently resistant to imatinib and other TKIs.

© Discovery Medicine

PMID: 19281912 [PubMed – indexed for MEDLINE] PMCID: PMC2782434 Free PMC Article