Epigenetic alteration of the SOCS1 gene in chronic myeloid leukaemia.
The expression of the suppressor of cytokine signalling-1 (SOCS1) protein is induced in response to stimulation by several cytokines. The induced SOCS1 inhibits the signalling pathway through the association with a variety of tyrosine kinase proteins. In this study, the mutation analyses, CpG island methylation status, and the expression of the SOCS1 gene in 112 chronic myeloid leukaemia (CML) samples, five leukaemia cell lines, and 30 normal controls were analysed. No genetic mutations of SOCS1 gene were noted in the CML samples. The SOCS1 gene was hypermethylated in 67% and 46% of the blastic and chronic phase CML samples respectively (P < 0.0001). However, there was no methylation of the SOCS1 gene in normal controls or CML in molecular remission. The methylation status of the SOCS1 gene is consistent with the results of the real-time quantitative reverse transcription polymerase chain reaction and immunocytochemistry staining. Our results demonstrate that the SOCS1 gene silencing is caused by the methylation of CpG islands in CML and is reversed to an unmethylated status in molecular remission. As SOCS1 has universal activity to negatively regulate several cytokine signalling pathways, the loss of the negative regulation of cytokine signalling by the SOCS1 may play a role in the pathogenesis of CML progression.
Liu
Ta-Chih
TC
Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. d730093@cc.kmu.edu.tw
Lin
Sheng-Fung
SF
Chang
Jan-Gowth
JG
Yang
Ming-Yu
MY
Hung
Shih-Ya
SY
Chang
Chao-Sung
CS
D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D018450:Disease Progression; D020868:Gene Silencing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins