p15 mRNA expression detected by real-time quantitative reverse transcriptase-polymerase chain reaction correlates with the methylation density of the gene in adult acute leukemia

Cyclin-dependent kinase inhibitor p15 is frequently inactivated by either methylation or deletion in patients with acute leukemia. To examine pathologic and clinical significance of the p15 gene inactivation, we established a quantitative assay of p15 mRNA expression in the bone marrow cells by real...

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Veröffentlicht in:Leukemia research 2005-05, Vol.29 (5), p.557-564
Hauptverfasser: Matsuno, Naofumi, Hoshino, Koyu, Nanri, Tomoko, Kawakita, Toshiro, Suzushima, Hitoshi, Kawano, Fumio, Mitsuya, Hiroaki, Asou, Norio
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container_end_page 564
container_issue 5
container_start_page 557
container_title Leukemia research
container_volume 29
creator Matsuno, Naofumi
Hoshino, Koyu
Nanri, Tomoko
Kawakita, Toshiro
Suzushima, Hitoshi
Kawano, Fumio
Mitsuya, Hiroaki
Asou, Norio
description Cyclin-dependent kinase inhibitor p15 is frequently inactivated by either methylation or deletion in patients with acute leukemia. To examine pathologic and clinical significance of the p15 gene inactivation, we established a quantitative assay of p15 mRNA expression in the bone marrow cells by real-time quantitative reverse transcriptase-polymerase chain reaction. p15 mRNA expression in 14 patients with precursor B-cell acute lymphoblastic leukemia (PBC-ALL) well correlated with status of deletion and methylation in the p15 gene analyzed by Southern blotting. Furthermore, two patients with PBC-ALL and 11 acute myeloblastic leukemia (AML) were quantitatively examined for p15 gene methylation using bisulfite genomic sequencing. The data showed that p15 mRNA expression significantly correlated with the CpG island methylation density. Among 108 AML patients, p15 mRNA expression was significantly lower in the myeloid lineage (M1, M2, M3) than the monocytic lineage (M4, M5) ( P = 0.0019). Above all, the majority of M3 patients showed low p15 expression compared with M1 and M2 patients ( P = 0.029). These observations suggest that quantitative analysis of p15 mRNA will be useful to evaluate transcriptional repression of the p15 gene caused by various degrees of methylation.
doi_str_mv 10.1016/j.leukres.2004.11.003
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To examine pathologic and clinical significance of the p15 gene inactivation, we established a quantitative assay of p15 mRNA expression in the bone marrow cells by real-time quantitative reverse transcriptase-polymerase chain reaction. p15 mRNA expression in 14 patients with precursor B-cell acute lymphoblastic leukemia (PBC-ALL) well correlated with status of deletion and methylation in the p15 gene analyzed by Southern blotting. Furthermore, two patients with PBC-ALL and 11 acute myeloblastic leukemia (AML) were quantitatively examined for p15 gene methylation using bisulfite genomic sequencing. The data showed that p15 mRNA expression significantly correlated with the CpG island methylation density. Among 108 AML patients, p15 mRNA expression was significantly lower in the myeloid lineage (M1, M2, M3) than the monocytic lineage (M4, M5) ( P = 0.0019). Above all, the majority of M3 patients showed low p15 expression compared with M1 and M2 patients ( P = 0.029). These observations suggest that quantitative analysis of p15 mRNA will be useful to evaluate transcriptional repression of the p15 gene caused by various degrees of methylation.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>15755508</pmid><doi>10.1016/j.leukres.2004.11.003</doi><tpages>8</tpages></addata></record>
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subjects Acute Disease
Adult
ALL
AML
Bone Marrow Cells - metabolism
Bone Marrow Cells - pathology
Burkitt Lymphoma - genetics
Burkitt Lymphoma - metabolism
Burkitt Lymphoma - pathology
Cell Cycle Proteins - genetics
Cell Lineage
CpG Islands
Cyclin-Dependent Kinase Inhibitor p15
DNA Methylation
Gene Expression Regulation, Leukemic
Humans
Leukemia, Myeloid - classification
Leukemia, Myeloid - genetics
Leukemia, Myeloid - metabolism
Methylation
p15
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - metabolism
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
RQ-PCR
Sequence Deletion
Tumor Cells, Cultured
Tumor Suppressor Proteins - genetics
title p15 mRNA expression detected by real-time quantitative reverse transcriptase-polymerase chain reaction correlates with the methylation density of the gene in adult acute leukemia
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