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Discovery of imatinib-responsive FIP1L1-PDGFRA mutation during refractory acute myeloid leukemia transformation of chronic myelomonocytic leukemia.

Abstract
The FIP1L1-PDGFRA rearrangement results in constitutive activation of the tyrosine kinase PDGFRA. Neoplasms harboring this rearrangement are responsive to imatinib mesylate at doses much lower than those recommended for the treatment of chronic myelogenous leukemia. Only a single report has described the identification of FIP1L1-PDGFRA in chronic myelomonocytic leukemia (CMML). Herein, we present a case report of a patient in whom the FIP1L1-PDGFRA was discovered as he evolved from CMML to acute myeloid leukemia (AML). The presence of a dominant neoplastic clone with FIP1L1-PDGFRA rearrangement was suspected on the basis of sudden onset of peripheral and bone marrow eosinophilia and confirmed by fluorescence in situ hybridization and molecular diagnostic tests. Whereas the patient was initially refractory to chemotherapy before the rearrangement was detected, subsequent therapy with imatinib led to complete remission.
AuthorsShilpan Shah, Sanam Loghavi, Guillermo Garcia-Manero, Joseph D Khoury
JournalJournal of hematology & oncology (J Hematol Oncol) Vol. 7 Pg. 26 (Mar 27 2014) ISSN: 1756-8722 [Electronic] England
PMID24669761 (Publication Type: Case Reports, Journal Article)
Chemical References
  • Benzamides
  • Oncogene Proteins, Fusion
  • Piperazines
  • Pyrimidines
  • mRNA Cleavage and Polyadenylation Factors
  • Imatinib Mesylate
  • FIP1L1-PDGFRA fusion protein, human
  • Receptor, Platelet-Derived Growth Factor alpha
Topics
  • Benzamides (administration & dosage, therapeutic use)
  • Eosinophilia (metabolism, pathology)
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myeloid, Acute (drug therapy, genetics, pathology)
  • Leukemia, Myelomonocytic, Chronic (drug therapy, genetics, pathology)
  • Male
  • Middle Aged
  • Mutation
  • Oncogene Proteins, Fusion (genetics, metabolism)
  • Piperazines (administration & dosage, therapeutic use)
  • Pyrimidines (administration & dosage, therapeutic use)
  • Receptor, Platelet-Derived Growth Factor alpha (genetics, metabolism)
  • Treatment Outcome
  • mRNA Cleavage and Polyadenylation Factors (genetics, metabolism)

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