Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders.
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.
David
Marianna
M
Department of Haematology, University of Pecs, Pecs, Hungary.
Cross
Nicholas C P
NC
Burgstaller
Sonja
S
Chase
Andrew
A
Curtis
Claire
C
Dang
Raymond
R
Gardembas
Martine
M
Goldman
John M
JM
Grand
Francis
F
Hughes
George
G
Huguet
Francoise
F
Lavender
Louise
L
McArthur
Grant A
GA
Mahon
Francois X
FX
Massimini
Giorgio
G
Melo
Junia
J
Rousselot
Philippe
P
Russell-Jones
Robin J
RJ
Seymour
John F
JF
Smith
Graeme
G
Stark
Alastair
A
Waghorn
Katherine
K
Nikolova
Zariana
Z
Apperley
Jane F
JF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004341:Drug Evaluation; D004802:Eosinophilia / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000097:blood*; D006801:Humans; D000068877:Imatinib Mesylate; D007223:Infant; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000097:blood* / Q000235:genetics; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000097:blood; D012334:RNA, Neoplasm / Q000097:blood; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000097:blood* / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic; D016896:Treatment Outcome; D000097764:ETS Translocation Variant 6 Protein
D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D016044:Fusion Proteins, bcr-abl; D000068877:Imatinib Mesylate; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D020797:Receptor, Platelet-Derived Growth Factor beta; C464679:ETV6-PDGFRB fusion protein, human; D000097764:ETS Translocation Variant 6 Protein