Subject(s)
Antineoplastic Agents/administration & dosage , Benzamides/administration & dosage , Eosinophilia/drug therapy , Leukemia, Myeloid/diagnosis , Leukemia, Myeloid/drug therapy , Oncogene Proteins, Fusion/isolation & purification , Piperazines/administration & dosage , Pyrimidines/administration & dosage , Receptor, Platelet-Derived Growth Factor alpha/isolation & purification , mRNA Cleavage and Polyadenylation Factors/isolation & purification , Humans , MaleABSTRACT
Obtaining a precise characterization of eosinophilia is crucial, as successful treatment relies on the underlying etiology of the disease. Platelet-derived growth factor receptor alpha-related disorders were first specified in 2008 as a distinct group of clonal eosinophilic disorders with exceptional responsiveness to imatinib. We herein present the case of a man with myeloid neoplasm and eosinophilia in whom a definitive diagnosis could not be adequately made based on histopathological features who was ultimately diagnosed only after extensive molecular analyses and successfully treated with imatinib. In addition, we discuss the diagnostic and therapeutic approaches to treating patients presenting with eosinophilia.
Subject(s)
Antineoplastic Agents/administration & dosage , Benzamides/administration & dosage , Eosinophilia/drug therapy , Leukemia, Myeloid/diagnosis , Leukemia, Myeloid/drug therapy , Oncogene Proteins, Fusion/isolation & purification , Piperazines/administration & dosage , Pyrimidines/administration & dosage , Receptor, Platelet-Derived Growth Factor alpha/isolation & purification , mRNA Cleavage and Polyadenylation Factors/isolation & purification , Adult , Eosinophilia/metabolism , Follow-Up Studies , Humans , Imatinib Mesylate , Leukemia, Myeloid/metabolism , Male , Oncogene Proteins, Fusion/drug effects , Oncogene Proteins, Fusion/metabolism , Receptor, Platelet-Derived Growth Factor alpha/drug effects , Receptor, Platelet-Derived Growth Factor alpha/metabolism , Treatment Outcome , mRNA Cleavage and Polyadenylation Factors/drug effects , mRNA Cleavage and Polyadenylation Factors/metabolismABSTRACT
Activated fibroblasts are thought to play important roles in the progression of many solid tumors, but little is known about the mechanisms responsible for the recruitment of fibroblasts in tumors. Using several methods, we identified platelet-derived growth factor A (PDGFA) as the major fibroblast chemoattractant and mitogen from conditioned medium generated by the Calu-6 lung carcinoma cell line. In addition, we showed that Calu-6 tumors express significant levels of PDGFC, and that the levels of expression of these two PDGFRalpha ligands correlate strongly with the degree of stromal fibroblast infiltration into the tumor mass. The most intense expression of PDGFRalpha was observed in fibroblasts in the tumor outer rim. We subsequently showed that disrupting PDGFRalpha-mediated signaling results in significant inhibition of tumor growth in vivo. Furthermore, analysis of a compendium of microarray data revealed significant expression of PDGFA, PDGFC, and PDGFRalpha in human lung tumors. We propose that therapies targeting this stromal cell type may be effective in treating certain types of solid tumors.
