PMID- 12842979
OWN - NLM
STAT- MEDLINE
DCOM- 20040105
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 102
IP  - 9
DP  - 2003 Nov 1
TI  - CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic 
      mastocytosis associated with eosinophilia and predicts response to imatinib 
      mesylate therapy.
PG  - 3093-6
AB  - Imatinib mesylate is effective in the treatment of hematologic malignancies that 
      are characterized by either abl- or PDGFR beta- activating mutations. The drug is 
      also active in a subset of patients with eosinophilic disorders and systemic mast 
      cell disease (SMCD). Recently, a novel tyrosine kinase that is generated from 
      fusion of the Fip1-like 1 (FIP1L1) and PDGFR alpha (PDGFRA) genes has been 
      identified as a therapeutic target for imatinib mesylate in hypereosinophilic 
      syndrome (HES). We used fluorescence in situ hybridization (FISH) to detect 
      deletion of the CHIC2 locus at 4q12 as a surrogate for the FIP1L1-PDGFRA fusion. 
      CHIC2 deletion was observed in bone marrow cells for 3 of 5 patients with SMCD 
      associated with eosinophilia. Deletion of this locus and expression of the 
      FIP1L1-platelet-derived growth factor receptor alpha (PDGFRA) fusion was also 
      documented in enriched eosinophils, neutrophils, or mononuclear cells by both 
      FISH and reverse transcriptase-polymerase chain reaction (RT-PCR) for one 
      patient. While all 3 patients with the FIP1L1-PDGFRA rearrangement achieved a 
      sustained complete response with imatinib mesylate therapy, the other two, both 
      carrying the c-kit Asp816 to Val (Asp816Val) mutation, did not. These 
      observations suggest that the FIP1L1-PDGFRA rearrangement occurs in an early 
      hematopoietic progenitor and suggests that the molecular pathogenesis for a 
      subset of SMCD patients is similar to that of HES. Screening for the 
      FIP1L1-PDGFRA rearrangement and Asp816Val mutation will advance rational therapy 
      decisions in SMCD.
FAU - Pardanani, Animesh
AU  - Pardanani A
AD  - Division of Hematology and Internal Medicine, Mayo Clinic, 200 First Street SW, 
      Rochester, MN 55905, USA.
FAU - Ketterling, Rhett P
AU  - Ketterling RP
FAU - Brockman, Stephanie R
AU  - Brockman SR
FAU - Flynn, Heather C
AU  - Flynn HC
FAU - Paternoster, Sarah F
AU  - Paternoster SF
FAU - Shearer, Brandon M
AU  - Shearer BM
FAU - Reeder, Terra L
AU  - Reeder TL
FAU - Li, Chin-Yang
AU  - Li CY
FAU - Cross, Nicholas C P
AU  - Cross NC
FAU - Cools, Jan
AU  - Cools J
FAU - Gilliland, D Gary
AU  - Gilliland DG
FAU - Dewald, Gordon W
AU  - Dewald GW
FAU - Tefferi, Ayalew
AU  - Tefferi A
LA  - eng
PT  - Journal Article
DEP - 20030703
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Benzamides)
RN  - 0 (FIP1L1 protein, human)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Piperazines)
RN  - 0 (Pyrimidines)
RN  - 0 (mRNA Cleavage and Polyadenylation Factors)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 2.7.10.1 (FIP1L1-PDGFRA fusion protein, human)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Benzamides
MH  - Eosinophilia/drug therapy/etiology/*genetics
MH  - Gene Rearrangement
MH  - Hematopoietic Stem Cells/pathology
MH  - Humans
MH  - Hypereosinophilic Syndrome/genetics
MH  - Imatinib Mesylate
MH  - In Situ Hybridization, Fluorescence
MH  - Mastocytosis, Systemic/complications/drug therapy/*genetics
MH  - Middle Aged
MH  - Oncogene Proteins, Fusion
MH  - Piperazines/*administration & dosage/therapeutic use
MH  - Predictive Value of Tests
MH  - Prospective Studies
MH  - Pyrimidines/*administration & dosage/therapeutic use
MH  - Receptor, Platelet-Derived Growth Factor alpha/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Sequence Deletion
MH  - Treatment Outcome
MH  - mRNA Cleavage and Polyadenylation Factors/*genetics
EDAT- 2003/07/05 05:00
MHDA- 2004/01/06 05:00
CRDT- 2003/07/05 05:00
PHST- 2003/07/05 05:00 [pubmed]
PHST- 2004/01/06 05:00 [medline]
PHST- 2003/07/05 05:00 [entrez]
AID - S0006-4971(20)53902-5 [pii]
AID - 10.1182/blood-2003-05-1627 [doi]
PST - ppublish
SO  - Blood. 2003 Nov 1;102(9):3093-6. doi: 10.1182/blood-2003-05-1627. Epub 2003 Jul 
      3.