[Study on abnormal expression of the p73 gene in childhood acute lymphoblastic leukemia].
OBJECTIVE
To investigate the relationship between p73 gene and the development and progression of childhood acute lymphoblastic leukemia (ALL).


METHODS
The levels of p73 transcripts in 61 ALL cell lines and 53 childhood ALL patients were assayed using reverse transcriptase-polymerase chain reaction (RT-PCR), and their relationship with the clinicopathological characteristics was analyzed. Besides, the methylation status of p73 exon 1 was analysed by restriction-enzyme related PCR, methylation-specific PCR and bisulfite genomic sequencing in the 61 ALL cell lines.


RESULTS
Of the 61 ALL cell lines, 42 showed expression of p73 mRNA, with a negative rate of 31.1%, and of the 53 primary childhood ALL samples, 39 showed expression of p73 mRNA, with a negative rate of 26.4%. Loss of p73 expression was significantly associated with the reduced disease free survival and overall survival of the patients. 39.3% (24/61) of the ALL cell lines showed hypermethylation of p73 exon 1, while normal lymphocytes and most cell lines expressed p73 mRNA were not hypermethylated.


CONCLUSIONS
There was a higher negative expression rate of p73 mRNA in childhood ALL. The main mechanism of the loss expression would be the hypermethylation of p73 gene. p73 gene inactivation might play an important role in the pathogenesis of ALL. Examination of p73 mRNA might have clinical significance in predicting prognosis of childhood ALL.
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
Mingli
M
Liu
Rongsheng
R
Li
Yasuhide
Y
Hayashi
Gujian
G
Zhu
Shanchun
S
Guo
D000293:Adolescent; D002460:Cell Line / Q000145:classification / Q000166:cytology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D007223:Infant; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D012333:RNA, Messenger / Q000096:biosynthesis; D015996:Survival Rate; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins