Epigenomic Changes during Leukemia Cell Differentiation: Analysis of Histone Acetylation and Cytosine Methylation Using CpG Island Microarrays

Nouzová, Marcela; Holtan, Nick; Oshiro, Marc M.; Isett, R. Benjamin; Muñoz-Rodríguez, José L.; List, Alan F.; Narro, Martha L.; Miller, Susan J.; Merchant, Nirav; Futscher, Bernard W.

doi:10.1124/jpet.104.072488

Cited by 71 publications

(75 citation statements)

References 32 publications

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“…In phase I of our two-phase strategy to characterize epigenetic phenomena in DLBCL, we measured DNA methylation levels in seven ABC-DLBCL and seven GCB-DLBCL tumors using CpG island microarray assays 12,16,17 (Figure 1). This provided a rapid means of evaluating the methylation-dependent cleavage of 442 unique gene-associated CpG islands by McrBC endonuclease (Supplementary Table 1 and Supplementary Figure 2).…”

Section: Resultsmentioning

confidence: 99%

“…12,13 Briefly, tumor DNA was digested with MseI and ligated to double-stranded linkers prior to division into equal test and reference fractions. The test fraction was digested with the methylation-dependent McrBC endonuclease (5 0 y Pu m C [N ] Pu m C y 3 0 ), while the reference fraction was untreated.…”

Section: Cpg Island Microarray Assaysmentioning

confidence: 99%

“…The amplified test and reference fractions were random prime labeled with Cy3-or Cy5-dUTP and combined in a cocktail prior to hybridization with CpG island microarrays. 12,13 Later, the microarrays were subjected to two washes, dried by centrifugation and imaged using the ScanArray 5000 (GSI Lumonics Inc., Boston, MA, USA) with ScanArray Express software (Perkin Elmer, Waltham, MA, USA). Signal intensities and quality metrics for each clone were calculated using ImaGene microarray software (BioDiscovery Inc., El Segundo, CA, USA).…”

Section: Cpg Island Microarray Assaysmentioning

confidence: 99%

“…12 Since mitochondrial DNA is unmethylated, 12,14 the signal intensities for both Cy3 and Cy5 are expected to be equal. Following normalization, the ratios of test and reference signals were calculated.…”

Section: Microarray Data Processingmentioning

confidence: 99%

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DNA methylation profiles in diffuse large B-cell lymphoma and their relationship to gene expression status

et al. 2008

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In an initial epigenetic characterization of diffuse large B-cell lymphoma (DLBCL), we evaluated the DNA methylation levels of over 500 CpG islands. Twelve CpG islands (AR, CDKN1C, DLC1, DRD2, GATA4, GDNF, GRIN2B, MTHFR, MYOD1, NEU-ROD1, ONECUT2 and TFAP2A) showed significant methylation in over 85% of tumors. Interestingly, the methylation levels of a CpG island proximal to FLJ21062 differed between the activated B-cell-like (ABC-DLBCL) and germinal center B-cell-like (GCB-DLBCL) subtypes. In addition, we compared the methylation and expression status of 67 genes proximal (within 500 bp) to the methylation assays. We frequently observed that hypermethylated CpG islands are proximal to genes that are expressed at low or undetectable levels in tumors. However, many of these same genes were also poorly expressed in DLBCL tumors where their cognate CpG islands were hypomethylated. Nevertheless, the proportional reductions in BNIP3, MGMT, RBP1, GATA4, IGSF4, CRABP1 and FLJ21062 expression with increasing methylation suggest that epigenetic processes strongly influence these genes. Lastly, the moderate expression of several genes proximal to hypermethylated CpG tracts suggests that DNA methylation assays are not always accurate predictors of gene silencing. Overall, further investigation of the highlighted CpG islands as potential clinical biomarkers is warranted.

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Section: Resultsmentioning

confidence: 99%

Section: Cpg Island Microarray Assaysmentioning

confidence: 99%

Section: Cpg Island Microarray Assaysmentioning

confidence: 99%

Section: Microarray Data Processingmentioning

confidence: 99%

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DNA methylation profiles in diffuse large B-cell lymphoma and their relationship to gene expression status

et al. 2008

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“…Furthermore, in de novo AML (compared to healthy controls) [21] or megakaryoblastic cell lines (compared to non-neoplastic CD34 + -derived megakaryoctic cells) [11], miRNA 10a is not differentially expressed, indicating that deregulation of miRNA 10a/HOXA1 homeostasis might be an event which could be restricted to the beginning phase of transformation and might require additional genetic or epigenetic deregulating events on the background of a leukaemic clone. For instance, at least in the promyelocytic leukaemia cell line NB4, the HOXA1 gene is epigenetically regulated by CpG methylation and histone acetylation [22], indicating that regulation by miRNA 10a might be only one of several mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Megakaryocytic expression of miRNA 10a, 17-5p, 20a and 126 in Philadelphia chromosome-negative myeloproliferative neoplasm

et al. 2008

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International audienceMicro RNA (miRNA) are small non-coding RNA molecules which have a post-transcriptional inhibitory regulation function, e.g. in megakaryopoiesis. A characteristic of Philadelphia chromosome-negative myeloproliferative neoplasm (Ph MPN) is the abundance of morphologically aberrant megakaryocytes. Based on previously published in vitro megakaryocytic differentiation assay data, we selected miRNA 10a, 17-5p, 20a and 126 and potential target proteins (HOXA1, RUNX1) for analysis of laser-microdissected bone marrow megakaryocytes from Ph MPN and controls ( = 66). Furthermore, we tested a potential influence of cytoreductive treatment on miRNA expression in bone marrow cells during the course of Ph MPN ( = 18). In summary, miRNA 17-5p, 20a and 126 are constitutively expressed in Ph MPN megakaryopoiesis while low or absent miRNA 10a appeared to correlate with strong megakaryocytic HOXA1 protein expression. No association to thrombocytosis, JAK2 mutations or cytoreductive treatment (bone marrow cells) were observed

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Acute Myeloid Leukemias

Valli¹

2007

Veterinary Comparative Hematopathology

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Epigenomic Changes during Leukemia Cell Differentiation: Analysis of Histone Acetylation and Cytosine Methylation Using CpG Island Microarrays

Cited by 71 publications

References 32 publications

DNA methylation profiles in diffuse large B-cell lymphoma and their relationship to gene expression status

DNA methylation profiles in diffuse large B-cell lymphoma and their relationship to gene expression status

Megakaryocytic expression of miRNA 10a, 17-5p, 20a and 126 in Philadelphia chromosome-negative myeloproliferative neoplasm

Acute Myeloid Leukemias

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