Abstract
P15INK4B methylation and expression was studied in bone marrow cells obtained from normal individuals, from patients who had been cured of lymphoma, and from patients with either MDS or AML. The level of p15 methylation was very low in normal BM cells and in CD34+ and CD34- subpopulations (0-6.5%; med, = 2.5%). P15INK4B transcripts were present in each of these cell populations. In contrast, methylation was the usual situation in MDS and AML marrows. The presence of methylation of the p15INK4B gene did not always indicate an absence of expression nor was expression always present if methylation was absent. P15INK4B methylation was studied in the marrows of nine patients (one studied twice) who had been cured of lymphoma and in whom hemopoiesis was believed to be normal. Increased methylaton was present in all 10 marrows. These data indicate that p15INK4B methylation is likely to be a very early event in the development of the secondary hematologic disorders.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Aged
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Antigens, CD34
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Bone Marrow Cells / metabolism
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Bone Marrow Cells / pathology
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Cell Cycle Proteins / genetics*
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Cyclin-Dependent Kinase Inhibitor p15
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Cyclin-Dependent Kinase Inhibitor p16 / genetics*
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DNA Methylation*
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Hematologic Diseases / genetics
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Hematologic Diseases / metabolism
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Humans
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Leukemia, Myeloid, Acute / genetics*
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Leukemia, Myeloid, Acute / metabolism
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Lymphoma / genetics*
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Lymphoma / metabolism
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Lymphoproliferative Disorders / genetics*
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Lymphoproliferative Disorders / metabolism*
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Middle Aged
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Myelodysplastic Syndromes / genetics*
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Myelodysplastic Syndromes / metabolism
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Neoplasms, Second Primary / genetics
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Neoplasms, Second Primary / metabolism
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RNA, Messenger / metabolism
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Remission Induction
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Tumor Suppressor Proteins*
Substances
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Antigens, CD34
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CDKN2B protein, human
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor p15
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Cyclin-Dependent Kinase Inhibitor p16
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RNA, Messenger
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Tumor Suppressor Proteins