Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders

Blood. 2007 Jan 1;109(1):61-4. doi: 10.1182/blood-2006-05-024828. Epub 2006 Sep 7.

Abstract

Fusion genes derived from the platelet-derived growth factor receptor beta (PDGFRB) or alpha (PDGFRA) play an important role in the pathogenesis of BCR-ABL-negative chronic myeloproliferative disorders (CMPDs). These fusion genes encode constitutively activated receptor tyrosine kinases that can be inhibited by imatinib. Twelve patients with BCR-ABL-negative CMPDs and reciprocal translocations involving PDGFRB received imatinib for a median of 47 months (range, 0.1-60 months). Eleven had prompt responses with normalization of peripheral-blood cell counts and disappearance of eosinophilia; 10 had complete resolution of cytogenetic abnormalities and decrease or disappearance of fusion transcripts as measured by reverse transcriptase-polymerase chain reaction (RT-PCR). Updates were sought from 8 further patients previously described in the literature; prompt responses were described in 7 and persist in 6. Our data show that durable hematologic and cytogenetic responses are achieved with imatinib in patients with PDGFRB fusion-positive, BCR-ABL-negative CMPDs.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Biomarkers, Tumor / blood
  • Child
  • Child, Preschool
  • Drug Evaluation
  • Eosinophilia / etiology
  • Female
  • Follow-Up Studies
  • Fusion Proteins, bcr-abl / blood*
  • Humans
  • Imatinib Mesylate
  • Infant
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / blood
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / drug therapy
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / genetics
  • Male
  • Middle Aged
  • Myeloproliferative Disorders / blood
  • Myeloproliferative Disorders / drug therapy*
  • Myeloproliferative Disorders / genetics
  • Oncogene Proteins, Fusion / blood*
  • Oncogene Proteins, Fusion / genetics
  • Piperazines / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / therapeutic use*
  • RNA, Messenger / blood
  • RNA, Neoplasm / blood
  • Receptor, Platelet-Derived Growth Factor beta / blood*
  • Receptor, Platelet-Derived Growth Factor beta / genetics
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Translocation, Genetic
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Benzamides
  • Biomarkers, Tumor
  • ETV6-PDGFRB fusion protein, human
  • Oncogene Proteins, Fusion
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • RNA, Messenger
  • RNA, Neoplasm
  • Imatinib Mesylate
  • Receptor, Platelet-Derived Growth Factor beta
  • Fusion Proteins, bcr-abl