Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta

N Engl J Med. 2002 Aug 15;347(7):481-7. doi: 10.1056/NEJMoa020150.


Background: A small proportion of patients with chronic myeloproliferative diseases have constitutive activation of the gene for platelet-derived growth factor receptor beta (PDGFRB), which encodes a receptor tyrosine kinase. The gene is located on chromosome 5q33, and the activation is usually caused by a t(5;12)(q33;p13) translocation associated with an ETV6-PDGFRB fusion gene. The tyrosine kinase inhibitor imatinib mesylate specifically inhibits ABL, PDGFR, and KIT kinases and has impressive clinical efficacy in BCR-ABL-positive chronic myeloid leukemia.

Methods: We treated four patients who had chronic myeloproliferative diseases and chromosomal translocations involving 5q33 with imatinib mesylate (400 mg daily). Three of the four patients presented with leukocytosis and eosinophilia; their leukemia cells carried the ETV6-PDGFRB fusion gene. The fourth patient had leukocytosis, eosinophilia, and a t(5;12) translocation involving PDGFRB and an unknown partner gene; he also had extensive raised, ulcerated skin lesions that had been present for a long time.

Results: In all four patients, a normal blood count was achieved within four weeks after treatment began. In the patient with skin disease, the lesions began to resolve shortly after treatment began. The t(5;12) translocation was undetectable by 12 weeks in three patients and by 36 weeks in the fourth patient. In the three patients with the ETV6-PDGFRB fusion gene, the transcript level decreased, and in one patient, it became undetectable by 36 weeks. All responses were durable at 9 to 12 months of follow-up.

Conclusions: Imatinib mesylate induces durable responses in patients with chronic myeloproliferative diseases associated with activation of PDGFRB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Benzamides
  • Child
  • Chromosomes, Human, Pair 5
  • DNA-Binding Proteins / genetics*
  • Eosinophilia / drug therapy
  • Gene Rearrangement
  • Humans
  • Imatinib Mesylate
  • In Situ Hybridization, Fluorescence
  • Leukocytosis / drug therapy
  • Male
  • Middle Aged
  • Myeloproliferative Disorders / drug therapy*
  • Myeloproliferative Disorders / genetics
  • Myeloproliferative Disorders / pathology
  • Oncogene Proteins, Fusion / genetics*
  • Piperazines / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-ets
  • Pyrimidines / therapeutic use*
  • Receptor, Platelet-Derived Growth Factor beta / genetics*
  • Repressor Proteins / genetics*


  • Benzamides
  • DNA-Binding Proteins
  • ETS translocation variant 6 protein
  • ETV6-PDGFRB fusion protein, human
  • Oncogene Proteins, Fusion
  • Piperazines
  • Proto-Oncogene Proteins c-ets
  • Pyrimidines
  • Repressor Proteins
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
  • Receptor, Platelet-Derived Growth Factor beta