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

Abstract

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.

• Authors: Jane F Apperley, Martine Gardembas, Junia V Melo, Robin Russell-Jones, Barbara J Bain, E Joanna Baxter, Andrew Chase, Judith M Chessells, Marie Colombat, Claire E Dearden, Sasa Dimitrijevic, François-X Mahon, David Marin, Zariana Nikolova, Eduardo Olavarria, Sandra Silberman, Beate Schultheis, Nicholas C P Cross, John M Goldman
• Journal: The New England journal of medicine (N Engl J Med) Vol. 347 Issue 7 Pg. 481-7 (Aug 15 2002) ISSN: 1533-4406 [Electronic] United States
• PMID: 12181402 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2002 Massachusetts Medical Society

Chemical References

• 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

Topics

• 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, genetics, 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)