Activity of STI571 in chronic myelomonocytic leukemia with a platelet-derived growth factor β receptor fusion oncogene

Platelet-derived growth factor p receptor (PDGFOR) fusion genes have been shown to be critical transforming oncogenes in a subset of patients with chronic myelomonocytic leukemia (CMML). The sensitivity of dysregulated tyrosine kinase oncogenes to the tyrosine kinase inhibitor ST1571 (imatinib mesylate) makes it a potentially attractive treatment option in this subset of patients. We have recently cloned a novel member of the PDGFOR fusion oncogene family, rabaptin-5PDGFbetaR. A patient with CMML carrying the rabaptin-5-PDGFbetaR fusion gene underwent allogeneic stem cell transplantation (SCT) and was monitored closely with a sensitive reverse transcriptasepolymerase chain assay to detect the novel fusion gene transcript. After achieving a molecular remission at 5 months after transplantation, 15 months after SCT the patient showed persistent and progressive evidence of molecular relapse. After demonstrating in vitro that cells transformed with this specific fusion oncogene are efficiently killed by ST1571, the patient was started on ST1571. The patient responded rapidly and entered molecular remission after 6 weeks of therapy, and he continues to be in remission 6 months later. These results suggest that ST1571 may be an effective targeted therapy in patients with CMML related to PDGFOR fusion oncogenes. (C) 2002 by The American Society of Hematology.