PMID- 12907457
OWN - NLM
STAT- MEDLINE
DCOM- 20040114
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 102
IP  - 12
DP  - 2003 Dec 1
TI  - Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated with 
      eosinophilia: involvement of PDGFRB and response to imatinib.
PG  - 4187-90
AB  - Eosinophilia is common in myeloproliferative disorders (MPDs) with abnormalities 
      of chromosome band 5q31-33, including those that present with t(1;5)(q23;q33). 
      With the development of rational drug therapy, characterization of the molecular 
      targets for these translocations could guide treatment and affect patient 
      survival. We cloned the t(1;5)(q23;q33) and showed that it fuses platelet-derived 
      growth factor receptor beta (PDGFRB) to the coiled-coil domains of a novel 
      partner protein, myomegalin. Using two-color interphase fluorescence in situ 
      hybridization (FISH), we also demonstrated that the eosinophils are clonal in 
      these disorders. Imatinib mesylate has recently been shown to be efficacious in 
      MPDs with PDGFR activation. Therefore, following our molecular studies, we were 
      able to redirect this patient's treatment. Although she had refractory and 
      progressive disease, once imatinib was started, complete clinical and hematologic 
      remission, as well as major cytogenetic response, was achieved. Given the 
      therapeutic implications, our findings stress the need to aggressively 
      investigate the molecular basis of these diseases, with emphasis on the PDGFR 
      family.
FAU - Wilkinson, Kathryn
AU  - Wilkinson K
AD  - Dana-Farber Cancer Institute, 44 Binney St, M514, Boston, MA 02115, USA.
FAU - Velloso, Elvira R P
AU  - Velloso ER
FAU - Lopes, Luiz Fernando
AU  - Lopes LF
FAU - Lee, Charles
AU  - Lee C
FAU - Aster, Jon C
AU  - Aster JC
FAU - Shipp, Margaret A
AU  - Shipp MA
FAU - Aguiar, Ricardo C T
AU  - Aguiar RC
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030807
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Benzamides)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Pde4dip protein, rat)
RN  - 0 (Piperazines)
RN  - 0 (Pyrimidines)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
SB  - IM
MH  - Benzamides
MH  - Chromosomes, Human, Pair 1
MH  - Chromosomes, Human, Pair 5
MH  - Clone Cells/pathology
MH  - Cloning, Molecular
MH  - Eosinophilia/*etiology/genetics/pathology
MH  - Female
MH  - Humans
MH  - Imatinib Mesylate
MH  - Infant
MH  - Microtubule-Associated Proteins/genetics
MH  - Myeloproliferative Disorders/complications/*drug therapy/*genetics
MH  - Piperazines/*therapeutic use
MH  - Pyrimidines/*therapeutic use
MH  - Receptor, Platelet-Derived Growth Factor beta/*genetics
MH  - Remission Induction
MH  - Translocation, Genetic
EDAT- 2003/08/09 05:00
MHDA- 2004/01/15 05:00
CRDT- 2003/08/09 05:00
PHST- 2003/08/09 05:00 [pubmed]
PHST- 2004/01/15 05:00 [medline]
PHST- 2003/08/09 05:00 [entrez]
AID - S0006-4971(20)44032-7 [pii]
AID - 10.1182/blood-2003-04-1150 [doi]
PST - ppublish
SO  - Blood. 2003 Dec 1;102(12):4187-90. doi: 10.1182/blood-2003-04-1150. Epub 2003 Aug 
      7.