Increased creatine kinase BB activity and CKB mRNA expression in patients with hematologic disorders: relation to methylation status of the CKB promoter.
BACKGROUND
We encountered 2 patients with increased activities of the creatine kinase (CK)-BB isoenzyme in their sera. Here we examined the relation among CK-BB activity, expression of CKB mRNA in peripheral blood, and hypermethylation of the CKB.


METHODS
The 2 patients and other 26 patients with hematologic malignancies, and some cancer cell lines were subjected to measurement of serum CK activity, CK isoenzyme analysis, CKB mRNA expression analysis by RT-PCR, and methylation analysis of the CKB promoter region.


RESULTS
CK-BB activity and proportion of leukemia blasts were correlated in the 2 patients. CKB mRNA was increased in peripheral blood during an increase in leukemia blast numbers. In contrast, none of the other 26 patients showed CK-BB activity or expression of CKB mRNA. In all of the patients with hematologic disorders, the analyzed region of CKB promoter was mostly unmethylated. However, some of cancer cell lines showed the methylated pattern. CKB mRNA was expressed at higher levels in cells with an unmethylated CKB promoter than in cells with a methylated promoter.


CONCLUSIONS
Expression of CKB mRNA and CK-B sometimes occurred in blastic transformation of the hematopoietic system. A relation between CKB mRNA expression and methylation of the CKB promoter was suggested.
Department of Laboratory Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
Jinko
J
Ishikawa
Terumi
T
Taniguchi
Akihiro
A
Takeshita
Masato
M
Maekawa
D001483:Base Sequence; D045744:Cell Line, Tumor; D052276:Creatine Kinase, BB Form / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007938:Leukemia / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D007527:Isoenzymes; D012333:RNA, Messenger; D052276:Creatine Kinase, BB Form