Expression of the leukemic prognostic marker CD7 is linked to epigenetic modifications in chronic myeloid leukemia.
BACKGROUND
Expression levels of the cell surface glycoprotein, CD7, and the serine protease, elastase 2 (ELA2), in the leukemic cells of patients with chronic myeloid leukemia (CML) have been associated with clinical outcome. However, little is known about the mechanisms that underlie the variable expression of these genes in the leukemic cells.


RESULTS
To address this question, we compared the level of their expression with the DNA methylation and histone acetylation status of 5' sequences of both genes in leukemic cell lines and primitive (lin-CD34+) leukemic cells from chronic phase CML patients. DNA methylation of the ELA2 gene promoter did not correlate with its expression pattern in lin-CD34+ cells from chronic phase CML patient samples even though there was clear differential DNA methylation of this locus in ELA2-expressing and non-expressing cell lines. In contrast, we found a strong relation between CD7 expression and transcription-permissive chromatin modifications, both at the level of DNA methylation and histone acetylation with evidence of hypomethylation of the CD7 promoter region in the lin-CD34+ cells from CML patients with high CD7 expression.


CONCLUSIONS
These findings indicate a link between epigenetic modifications and CD7 expression in primitive CML cells.
Rogers
Sally L
SL
Terry Fox Laboratory, British Columbia Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada. srogers@bccrc.ca
Zhao
Yun
Y
Jiang
Xiaoyan
X
Eaves
Connie J
CJ
Mager
Dixie L
DL
Rouhi
Arefeh
A
D000107:Acetylation; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D019011:Antigens, CD7 / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006657:Histones / Q000378:metabolism; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D018952:Antigens, CD34; D019011:Antigens, CD7; D014408:Biomarkers, Tumor; D006657:Histones; D012333:RNA, Messenger; D012697:Serine Endopeptidases; C117309:pancreatic elastase II