Open AccessMolecular framework for response to imatinib mesylate in systemic sclerosis
Author(s) -
Chung Lorinda,
Fiorentino David F.,
BenBarak Maya J.,
Adler Adam S.,
Mariano Melissa M.,
Paniagua Ricardo T.,
Milano Ausra,
Connolly M. Kari,
Ratiner Boris D.,
Wiskocil Robert L.,
Whitfield Michael L.,
Chang Howard Y.,
Robinson William H.
Publication year - 2009
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.24221
Subject(s) - imatinib mesylate , imatinib , medicine , tyrosine kinase inhibitor , tyrosine kinase , platelet derived growth factor receptor , cancer research , abl , pathogenesis , immunology , pathology , receptor , growth factor , cancer , myeloid leukemia
Systemic sclerosis (SSc) is an autoimmune disease in which the tyrosine kinases platelet‐derived growth factor receptor (PDGFR) and Abl are hypothesized to contribute to the fibrosis and vasculopathy of the skin and internal organs. Herein we describe 2 patients with early diffuse cutaneous SSc (dcSSc) who experienced reductions in cutaneous sclerosis in response to therapy with the tyrosine kinase inhibitor imatinib mesylate. Immunohistochemical analyses of skin biopsy specimens demonstrated reductions of phosphorylated PDGFRβ and Abl with imatinib therapy. By gene expression profiling, an imatinib‐responsive signature specific to dcSSc was identified ( P < 10 −8 ). The response of these patients and the findings of the analyses suggest that PDGFRβ and Abl play critical, synergistic roles in the pathogenesis of SSc, and that imatinib targets a gene expression program that is frequently dysregulated in dcSSc.