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Prepublished online as a Blood First Edition Paper on May 13, 2002; DOI 10.1182/blood-2001-11-0026.

Submitted November 26, 2001
Accepted April 27, 2002
Aberrant DNA methylation of p57KIP2 gene in the promoter region in lymphoid malignancies of B-cell phenotype
YINGHUA LI, HIROKAZU NAGAI*, TOSHIHITO OHNO, MASAAKI YUGE, SONOKO HATANO, ETSURO ITO, NAOYOSHI MORI, HIDEHIKO SAITO, and TOMOHIRO KINOSHITA
Ist DEPARTMENT OF INTERNAL MEDICINE, NAGOYA UNIVERSITY SCHOOL OF MEDICINE, NAGOYA, Japan; DEPARTMENT OF HEMATOLOGY, NAGOYA NATIONAL HOSPITAL, NAGOYA, Japan
DEPARTMENT OF HEMATOLOGY, NAGOYA NATIONAL HOSPITAL, NAGOYA, Japan; Ist DEPARTMENT OF INTERNAL MEDICINE, NAGOYA UNIVERSITY SCHOOL OF MEDICINE, NAGOYA, Japan
Ist DEPARTMENT OF INTERNAL MEDICINE, NAGOYA UNIVERSITY SCHOOL OF MEDICINE, NAGOYA, Japan
DEPARTMENT OF PEDIATRICS, SCHOOL OF MEDICINE HIROSAKI UNIVERSITY, HIROSAKI, Japan
Ist DEPARTMENT OF PATHOLOGY, NAGOYA UNIVERSITY SCHOOL OF MEDICINE, NAGOYA, Japan
DEPARTMENT OF HEMATOLOGY, NAGOYA NATIONAL HOSPITAL, NAGOYA, Japan; Ist DEPARTMENT OF INTERNAL MEDICINE, NAGOYA UNIVERSITY SCHOOL OF MEDICINE, NAGOYA, Japan; AICHI BLOOD DISEASE RESEARCH FOUNDATION, NAGOYA, Japan
* Corresponding author; email: nagaih{at}nnh.hosp.go.jp.
The cyclin-dependent kinase (CDK) inhibitor p57KIP2, is thought to be a potential tumor suppressor gene (TSG). The present study examines this possibility. We found that the expression of p57KIP2 gene is absent in various hematological cell lines. Exposing cell lines to the DNA demethylating agent, 5-aza-2[[rad]]-deoxycytidine, restored p57KIP2 gene expression. Bisulfite sequencing analysis of its promoter region showed that p57KIP2 DNA was completely methylated in cell lines that did not express the p57KIP2 gene. Thus, DNA methylation of its promoter might lead to inactivation of the p57KIP2 gene. DNA methylation of this region is thought to be an aberrant alteration, since DNA was not methylated in normal peripheral blood mononuclear cells and in reactive lymphadenitis. Methylation-specific PCR analysis found frequent DNA methylation of the p57KIP2 gene in primary diffuse large B cell lymphoma (54.9%) and in follicular lymphoma (44.0%), but methylation was infrequent in myelodysplastic syndrome and adult T cell leukemia (3.0% and 2.0% respectively). These findings directly indicate that the profile of the p57KIP2 gene fits that of a TSG.

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