[Identification of FIP1L1-PDGFRA fusion, and expression of signal transducer and activator of transcription 5 in hypereosinophilic syndrome].
OBJECTIVE
To determine whether FIP1L1-PDGFRA fusion exists in hypereosinophilic syndrome (HES) patients, explore the relationship between FIP1L1-PDGFRA fusion and clinical phenotypes, and observe and reveal the expression of signal transducer and activator of transcription 5 (STAT(5)) in granulocytes of HES and the biological significance thereof.


METHODS
Specimens of peripheral blood were collected from 4 HES patients diagnosed based on the criteria of Chusid et al. Total RNA was extracted from granulocytes and cDNA was synthesized by reverse transcription. Nested-PCR was used to amplify the target fusion gene and the positive PCR fragments were sequenced directly. Total protein of the peripheral granulocytes was extracted. Western blotting was used to detect the expression of STAT(5) protein in the granulocyte lysates.


RESULTS
FIP1L1-PDGFRA fusion genes were found in 3 of the 4 HES patients. The break points in PDGFRA were all located at exon 12, while in FIP1L1 the break points were highly variable, located at exon 8a, intron 8a, and exon 8 respectively. The patients with FIP1L1-PDGFRA fusion were susceptible to cardiac involvement. The expression of STAT(5) protein was upregulated in FIP1L1-PDGFRA positive HES patients, while STAT(5) protein expression was negative in HES patients without FIP1L1-PDGFRA fusion.


CONCLUSIONS
FIP1L1-PDGFRA fusion has a universal significance for HES. The identification of FIP1L1-PDGFRA rearrangement is a useful molecular mark for HES diagnosis and works as the therapeutic target of imatinib. Furthermore, the activation of STAT(5), a downstream signal of the FIP1L1-PDGFRA fusion, indicates that HES is a malignant clonal disease of the hematopoietic tissue.
Zhang
Guang-Sen
GS
Department of Hematology, Institute of Molecular Hematology, the Second Xiangya Hospital, Central South University, Changsha 410011, China.
Li
Bin
B
Pei
Min-Fei
MF
Dai
Chong-Wen
CW
Zheng
Wen-Li
WL
Shen
Jian-Kai
JK
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008894:Milk Proteins / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000096:biosynthesis / Q000235:genetics*; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*; D039221:mRNA Cleavage and Polyadenylation Factors / Q000096:biosynthesis / Q000235:genetics*
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D015514:Oncogene Proteins, Fusion; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D039221:mRNA Cleavage and Polyadenylation Factors; C479819:FIP1L1-PDGFRA fusion protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha