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Blood, 1 May 2001, Vol. 97, No. 9, pp. 2823-2829
NEOPLASIA
Methylation profiling in acute myeloid leukemia
Minoru Toyota,
Kenneth J. Kopecky,
Mutsumi-Ohe Toyota,
Kam-Wing Jair,
Cheryl L. Willman, and
Jean-Pierre J. Issa
From the Johns Hopkins Oncology Center, Baltimore, MD;
the University of New Mexico School of Medicine, Albuquerque, NM; the
Southwest Oncology Group Statistical Center, Seattle, WA; and the
Leukemia Department, University of Texas at MD Anderson Cancer Center,
Houston, TX.
Aberrant methylation of multiple CpG islands has been described in
acute myeloid leukemia (AML), but it is not known whether these are
independent events or whether they reflect specific methylation
defects in a subset of cases. To study this issue, the
methylation status of 14 promoter-associated CpG islands was analyzed
in 36 cases of AML previously characterized for
estrogen-receptor methylation (ERM). Cases with methylation
density of 10% or greater were considered positive. Seventeen cases
(47%) were ERM+ while 19 cases were
ERM . Hypermethylation of any of the following,
p15, p16, CACNA1G, MINT1, MINT2, MDR1,
THBS1, and PTC1 (2 promoters), was relatively infrequent (6% to 31% of patients). For each of these CpG islands, the methylation density was positively correlated with ERM density (rank order correlation coefficients, 0.32-0.59; 2-tailed
P  .058 for each gene). Hypermethylation of
MYOD1, PITX2, GPR37, and
SDC4 was frequently found in AML (47% to 64% of
patients). For each of these genes as well, methylation density was
positively correlated with ERM density (correlation coefficients 0.43 to 0.69, P .0087 for each gene). MLH1 was
unmethylated in all cases. Hypermethylation of p15,
MDR1, and SDC4 correlated with reduced levels
of expression. There was an inverse correlation between age and the
number of genes methylated (P = .0030). It was concluded that CpG-island methylation in AML results from methylation defects in
subsets of cases. These results have potential implications for the
classification and prognosis of AML and for the identification of
patients who may benefit from treatment with methylation inhibitors.
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|
|
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|
|
|
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[Full Text]
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|
|
|
|
|
|
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|
|
|
|
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|
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|
|
|
|
|
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|
|
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|
|
|
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|
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|
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|
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|
|
|
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|
|
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|
|
|
|
|
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23(17):
3886 - 3896.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.G. HERMAN
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[Abstract]
[PDF]
|
|
|
|
|
|
|
J. D. Licht and D. W. Sternberg
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January 1, 2005;
2005(1):
137 - 142.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Nagasaka, H. Sasamoto, K. Notohara, H. M. Cullings, M. Takeda, K. Kimura, T. Kambara, D. G. MacPhee, J. Young, B. A. Leggett, et al.
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22(22):
4584 - 4594.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
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P. M. Das and R. Singal
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22(22):
4632 - 4642.
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|
|
|
|
|
|
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10(13):
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Kondo, L. Shen, P. S. Yan, T. H.-M. Huang, and J.-P. J. Issa
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May 11, 2004;
101(19):
7398 - 7403.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Takahashi, N. Shivapurkar, J. Reddy, H. Shigematsu, K. Miyajima, M. Suzuki, S. Toyooka, S. Zochbauer-Muller, J. Drach, G. Parikh, et al.
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10(9):
2928 - 2935.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. C. Malins, K. M. Anderson, N. L. Polissar, G. K. Ostrander, E. T. Knobbe, V. M. Green, N. K. Gilman, and J. L. Spivak
Models of granulocyte DNA structure are highly predictive of myelodysplastic syndrome
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April 6, 2004;
101(14):
5008 - 5011.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Zheng, X. Ma, L. Zhang, L. Gunn, M. T. Smith, J. L. Wiemels, K. Leung, P. A. Buffler, and J. K. Wiencke
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March 15, 2004;
64(6):
2000 - 2006.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-P. J. Issa, G. Garcia-Manero, F. J. Giles, R. Mannari, D. Thomas, S. Faderl, E. Bayar, J. Lyons, C. S. Rosenfeld, J. Cortes, et al.
Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in hematopoietic malignancies
Blood,
March 1, 2004;
103(5):
1635 - 1640.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. T. Voso, A. Scardocci, F. Guidi, G. Zini, A. Di Mario, L. Pagano, S. Hohaus, and G. Leone
Aberrant methylation of DAP-kinase in therapy-related acute myeloid leukemia and myelodysplastic syndromes
Blood,
January 15, 2004;
103(2):
698 - 700.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. F. List, J. Vardiman, J.-P. J. Issa, and T. M. DeWitte
Myelodysplastic Syndromes
Hematology,
January 1, 2004;
2004(1):
297 - 317.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-P. J. Issa
Methylation and Prognosis: Of Molecular Clocks and Hypermethylator Phenotypes
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August 1, 2003;
9(8):
2879 - 2881.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Ogi, M. Toyota, M. Ohe-Toyota, N. Tanaka, M. Noguchi, T. Sonoda, G. Kohama, and T. Tokino
Aberrant Methylation of Multiple Genes and Clinicopathological Features in Oral Squamous Cell Carcinoma
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October 1, 2002;
8(10):
3164 - 3171.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Daskalakis, T. T. Nguyen, C. Nguyen, P. Guldberg, G. Kohler, P. Wijermans, P. A. Jones, and M. Lubbert
Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-Aza-2'-deoxycytidine (decitabine) treatment
Blood,
September 26, 2002;
100(8):
2957 - 2964.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Garcia-Manero, J. Daniel, T. L. Smith, S. M. Kornblau, M.-S. Lee, H. M. Kantarjian, and J.-P. J. Issa
DNA Methylation of Multiple Promoter-associated CpG Islands in Adult Acute Lymphocytic Leukemia
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July 1, 2002;
8(7):
2217 - 2224.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
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Clin. Cancer Res.,
June 1, 2002;
8(6):
1897 - 1903.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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DNA Methylation and Environmental Exposures in Human Hepatocellular Carcinoma
J Natl Cancer Inst,
May 15, 2002;
94(10):
755 - 761.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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5' CpG island hypermethylation is associated with transcriptional silencing of the p21CIP1/WAF1/SDI1 gene and confers poor prognosis in acute lymphoblastic leukemia
Blood,
April 1, 2002;
99(7):
2291 - 2296.
[Abstract]
[Full Text]
[PDF]
|
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