Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta.
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.
Apperley
Jane F
JF
Department of Haematology, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom. j.apperley@ic.ac.uk
Gardembas
Martine
M
Melo
Junia V
JV
Russell-Jones
Robin
R
Bain
Barbara J
BJ
Baxter
E Joanna
EJ
Chase
Andrew
A
Chessells
Judith M
JM
Colombat
Marie
M
Dearden
Claire E
CE
Dimitrijevic
Sasa
S
Mahon
François-X
FX
Marin
David
D
Nikolova
Zariana
Z
Olavarria
Eduardo
E
Silberman
Sandra
S
Schultheis
Beate
B
Cross
Nicholas C P
NC
Goldman
John M
JM
D000328:Adult; D000368:Aged; D001549:Benzamides; D002648:Child; D002895:Chromosomes, Human, Pair 5; D004268:DNA-Binding Proteins / Q000235:genetics*; D004802:Eosinophilia / Q000188:drug therapy; D015321:Gene Rearrangement; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D007964:Leukocytosis / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D050783:Proto-Oncogene Proteins c-ets; D011743:Pyrimidines / Q000627:therapeutic use*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D000097764:ETS Translocation Variant 6 Protein
D001549:Benzamides; D004268:DNA-Binding Proteins; D000068877:Imatinib Mesylate; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D011505:Protein-Tyrosine Kinases; D050783:Proto-Oncogene Proteins c-ets; D011743:Pyrimidines; D020797:Receptor, Platelet-Derived Growth Factor beta; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C464679:ETV6-PDGFRB fusion protein, human