SOCS1 methylation in patients with newly diagnosed acute myeloid leukemia.
The proliferation and differentiation of hematopoietic precursor cells depend on various cytokines. The suppressor of cytokine signaling-1 (SOCS1) down-regulates Janus kinases/signal transducers and activators of transcription (JAK/STAT) pathway activity and inhibits the biological effects of cytokines. SOCS1 has been shown to have tumor-suppressor activity, and methylation of this gene, resulting in transcriptional silencing, has been found in 65% of hepatocellular carcinoma and has been suggested to play an important role in the development of the cancer. The methylation status of the SOCS1 gene in acute myeloid leukemia (AML) has not been reported before. In this study, we analyzed SOCS1 methylation in 89 patients with newly diagnosed AML and correlated the result with immunophenotypes, cytogenetics, clinical features, and treatment outcome. SOCS1 methylation was found in the leukemic cells from 53 patients (60%). Thirteen (76%) of the 17 patients with t(15;17) had SOCS1 methylation, whereas this gene was methylated in only one (11%) of the nine patients with t(8;21). The frequencies of SOCS1 methylation among various cytogenetic subgroups differed significantly (P = 0.014). Other clinical and laboratory parameters and the disease-free survival and overall survival were similar between patients with and without SOCS1 methylation. In conclusion, SOCS1 methylation occurs in more than half of AML cases, correlates with cytogenetic abnormalities, and may play an important role in the development of subsets of AML.
Chen
Chien-Yuan
CY
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Tsay
Woei
W
Tang
Jih-Luh
JL
Shen
Hwei-Ling
HL
Lin
Shu-Wha
SW
Huang
Sheng-Yi
SY
Yao
Ming
M
Chen
Yao-Chang
YC
Shen
Ming-Ching
MC
Wang
Chiu-Hwa
CH
Tien
Hwei-Fang
HF
D001854:Bone Marrow Cells / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D020732:Cytogenetic Analysis; D019175:DNA Methylation; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D047908:Intracellular Signaling Peptides and Proteins; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012097:Repressor Proteins; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016896:Treatment Outcome
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