Level of HOXA5 hypermethylation in acute myeloid leukemia is associated with short-term outcome.
Hypermethylation of the homeobox (HOX) gene promoter leads to decreased expression of the gene during tumor development and is thought to be correlated with the clinical outcome in leukemia. In this study, we performed pyrosequencing to quantify the methylation level of HOXA5 genes in the bone marrow samples obtained from 50 patients with AML and 19 normal controls. The methylation percentage of HOXA5 in AML patients (median=65.4%, interquartile range=35.9-72.3%) was higher than that of HOXA5 in control patients (median=43.1%, interquartile range=36.7-49.6%, Mann-Whitney U test, P=0.012). The patients of the AML group who had a high methylation percentage (>70%) had a good prognosis with a 3-yr overall survival (OS) of 82.5%, whereas the patients with a low methylation percentage (≤70%) showed a 3-yr OS of 40.5% (P=0.048). Cox proportional hazards regression showed that the methylation percentages of HOXA5 were independently associated with the 3-yr OS of AML patients, regardless of their karyotypes. We propose that the quantification of HOXA5 methylation by pyrosequencing may be useful for predicting short-term prognosis in AML. However, the limitations of our study are the small sample size and its preliminary nature. Thus, a larger study should be performed to clearly determine the relationships among HOXA5 methylation levels, cytogenetics, and prognosis in AML patients.
Kim
Shine Young
SY
Department of Laboratory Medicine, Pusan National University School of Medicine, Busan, Korea.
Hwang
Sang-Hyun
SH
Song
Eun Joo
EJ
Shin
Ho Jin
HJ
Jung
Joo Seop
JS
Lee
Eun Yup
EY
D000328:Adult; D000368:Aged; D019175:DNA Methylation; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D017422:Sequence Analysis, DNA; D015996:Survival Rate
C489213:HOXA5 protein, human; D018398:Homeodomain Proteins