JOURNAL ARTICLE

[The activation of JAK/STAT signal pathway in hypereosinophilic syndrome and the patients therapeutic response to imatinib]

Bin Li, Guang-Sen Zhang, Chong-Wen Dai, Min-Fei Pei
Zhonghua Yi Xue za Zhi [Chinese medical journal] 2005 February 23, 85 (7): 448-52
15854548

OBJECTIVE: To determine whether JAK/STAT pathway is involved in proliferation of hypereosinophilic syndrome (HES) cells, and reveal the pathogenesis of HES; observe the dynamic change of the clinical phenotype and hematological response, the expression of janaus kinase/signal transducer and activator of transcription (JAK/STAT) protein or FIP1L1-PDGFRA mRNA in one HES patient treated with low-dose imatinib.

METHODS: The granulocytes of peripheral blood of 4 HES patients, including 3 FIP1L1-PDGFRA positive cases and 1 negative case, were collected. The expression of JAK2, STAT3, and phosphorylated STAT (P-STAT5) proteins were detected by western blotting. One FIP1L1-PDGFRA fusion gene positive patient was administered with low-dose imatinib. Retrospective reverse transcription polymerase chain reaction (RT-PCR) analysis of FIP1L1-PDGFRA was performed and the expressions of JAK2, STAT3 and P-STAT5 were detected by western blotting before treatment and 10, 30, and 60 days after the beginning of treatment.

RESULTS: Upregulation of JAK2, STAT3, and P-STAT5 proteins was shown in 3 FIP1L1-PDGFRA fusion gene positive HES patients, while all of these proteins were not expressed in one case of FIP1L1-PDGFRA negative HES. Continuous hematological remission was observed in one FIP1L1-PDGFRA fusion gene positive HES patient after low-dose imatinib treatment. The amount of FIP1L1-PDGFRA transcripts in peripheral blood granulocytes was significantly decreased in 30 days after therapy and turned negative 60 days after therapy. JAK2, STAT3, STAT5, and P-STAT5 expressions were all down-regulated time-dependently and were all negative 60 days after.

CONCLUSION: There is excessive activation of JAK/STAT signal pathway in HES patient, which may contribute to the malignant proliferation of eosinophils. Low-dose imatinib, that induces complete hematological and molecular genetic remission, exerts significant effects on FIP1L1-PDGFRA positive HES.

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