Hypermethylation of DLX4 predicts poor clinical outcome in patients with myelodysplastic syndrome.
BACKGROUND
Hypermethylation of DLX4 (distal-less homeobox 4) has been disclosed in a variety of cancers. Our work was aimed to examine the pattern of DLX4 methylation and further investigate its clinical relevance in patients with myelodysplastic syndrome (MDS).


METHODS
Real-time quantitative methylation-specific PCR and bisulfite sequencing PCR were carried out to detect the level of DLX4 methylation. Clinical significance of DLX4 methylation was analyzed between the DLX4 hypermethylated and non-hypermethylated patients.


RESULTS
DLX4 was significantly hypermethylated in MDS patients than controls (p<0.001). No significant differences were observed between the hypermethylated and non-hypermethylated MDS patients in white blood cells, platelets, age, WHO classifications, FAB classifications, IPSS risks, and common gene mutations (p>0.05). However, DLX4 hypermethylated patients tended to have higher hemoglobin (HB) than DLX4 non-hypermethylated patients (p=0.079). Moreover, there was a trend that male patients, poor karyotype patients, and IPSS Int-2/High patients had a higher frequency of DLX4 hypermethylation (p=0.067, 0.065, and 0.068). DLX4 hypermethylated patients had significantly shorter overall survival than DLX4 non-hypermethylated patients (p=0.004). Multivariate analysis confirmed the prognostic value of DLX4 methylation in MDS patients (p<0.001).


CONCLUSIONS
Our study indicated that DLX4 hypermethylation was a frequent event and acted as an independent prognostic biomarker in de novo MDS patients.
Ting-Juan
TJ
Zhang
Jing-Dong
JD
Zhou
Dong-Qin
DQ
Yang
Yu-Xin
YX
Wang
Dong-Ming
DM
Yao
Ji-Chun
JC
Ma
Xiang-Mei
XM
Wen
Hong
H
Guo
Jiang
J
Lin
Jun
J
Qian
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D015331:Cohort Studies; D019175:DNA Methylation; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis* / Q000235:genetics*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
D015415:Biomarkers; C105304:DLX4 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors