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Blood, Vol. 95 No. 9 (May 1), 2000:
pp. 2990-2992
BRIEF REPORT
Quantitative measure of c-abl and
p15 methylation in chronic myelogenous leukemia: biological
implications
TuDung T. Nguyen,
Ann F. Mohrbacher,
Yvonne C. Tsai,
John Groffen,
Nora Heisterkamp,
Peter
W. Nichols,
Mimi C. Yu,
Michael Lübbert, and
Peter A. Jones
From the Departments of Biochemistry & Molecular
Biology; Hematology/Oncology; Pathology; and Preventive Medicine,
USC/Norris Cancer Center, University of Southern California, Los
Angeles, CA; the Division of Hematology/Oncology,
Children's Hospital, Los Angeles, CA; and the Division of
Hematology/Oncology, the Medical University of Freiburg Medical Center,
Freiburg, Germany.
We used a sensitive, quantitative bisulfite PCR assay, methylation
sensitive single nucleotide primer extension (Ms-SNuPE), to
measure methylation of the 5' CpG islands of c-abl and
p15 in chronic myelogenous leukemia (CML) patients during
progression. We found that the Pa promoter of c-abl was
methylated in 81% (17/21) of the white blood cells (WBCs) of CML
patients, which correlates with previous reports. In contrast, WBCs
from healthy donors, acute myelogenous leukemias, acute lymphocytic
leukemias, and myelodysplastic syndromes were unmethylated at the
c-abl Pa promoter locus. We also observed p15
hypermethylation in 24% (8/34) of CML cases. Methylation of the
p15 but not c-abl Pa promoters was associated with CML
progression (P = 0.047 vs 0.46), and the two events were
independently acquired. We conclude that de novo methylation of
c-abl and p15 both occur in CML, and analysis of DNA
methylation changes using the bisulfite-based MS-SNuPE assay allows
both a sensitive and quantitative assessment of these molecular events compared to other methods currently utilized.

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