ID4 methylation predicts high risk of leukemic transformation in patients with myelodysplastic syndrome.
Epigenetic gene silencing due to promoter methylation is observed in human cancers like acute myeloid leukemia (AML). Little is known about aberrant methylation in myelodysplastic syndrome (MDS), a heterogeneous clonal stem cell disorder with a approximately 30% risk of transformation into secondary AML. Recent evidence demonstrated that ID4, a negative regulator of transcription, may act as a tumor-suppressor gene. To clarify the role of ID4 in MDS, we employed methylation-specific PCR (MSP) to examine the methylation status of ID4 in 144 adult de novo MDS patients. We found that ID4 methylation was present in 35.4% (n=51) of these MDS patients and methylaiton was correlated significantly with World Health Organization (WHO) subtypes and International Prognostic Scoring System (IPSS) risk groups. Patients with advanced stages of WHO subtypes (45.8% vs. 21.3%, P=0.002) and higher risk IPSS subgroups (45.7% vs. 26.0%, P=0.014) exhibited a significantly higher frequency of ID4 methylation. The median survival of patients with ID4 methylation was shorter than patients without ID4 methylation (12.2 months vs. 26.9 months, P=0.005). Multivariate analysis indicated that ID4 methylation status was the independent factor that impacted leukemia-free survival (LFS). Disease in patients with ID4 methylation progressed more rapidly than those without ID4 methylation (P=0.047, HR=2.11). Our results suggest that ID4 may be a therapeutic target in MDS.
Wang
Hong
H
Department of Haematology, Huashan Hospital of Fudan University, 12 Wulumuqi Road Central, 200040 Shanghai, China.
Wang
Xiao-Qin
XQ
Xu
Xiao-Ping
XP
Lin
Guo-Wei
GW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000401:mortality; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012307:Risk Factors; D055815:Young Adult
C490128:ID4 protein, human; D051796:Inhibitor of Differentiation Proteins