Quantitative measure of c-abl and p15 methylation in chronic myelogenous leukemia : biological implications

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...

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Bibliographic Details
Published in:Blood 2000-05, Vol.95 (9), p.2990-2992
Main Authors: NGUYEN, T. T, MOHRBACHER, A. F, TSAI, Y. C, GROFFEN, J, HEISTERKAMP, N, NICHOLS, P. W, YU, M. C, LÜBBERT, M, JONES, P. A
Format: Article
Language:English
Subjects:
Biological and medical sciences
Blast Crisis
Carrier Proteins - genetics
Cell Cycle Proteins
Cyclin-Dependent Kinase Inhibitor p15
Cyclin-Dependent Kinase Inhibitor p16
DNA Methylation
Genes, abl
Genes, Tumor Suppressor
Hematologic and hematopoietic diseases
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - blood
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Medical sciences
Promoter Regions, Genetic
Proto-Oncogene Proteins c-abl - genetics
Tumor Suppressor Proteins
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Summary: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. (Blood. 2000;95:2990-2992)
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.v95.9.2990.009k08_2990_2992