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dc.contributor.authorHalldórsdóttir, Anna Margrét
dc.contributor.authorKanduri, Meena
dc.contributor.authorMarincevic, Millaray
dc.contributor.authorMansouri, Larry
dc.contributor.authorIsaksson, Anders
dc.contributor.authorGöransson, Hanna
dc.contributor.authorAxelsson, Tomas
dc.contributor.authorAgarwal, Prasoon
dc.contributor.authorJernberg-Wiklund, Helena
dc.contributor.authorStamatopoulos, Kostas
dc.contributor.authorSander, Birgitta
dc.contributor.authorEhrencrona, Hans
dc.contributor.authorRosenquist, Richard
dc.date.accessioned2013-08-16T13:33:55Z
dc.date.available2013-08-16T13:33:55Z
dc.date.issued2012-04
dc.date.submitted2013-08-16
dc.identifier.citationAm. J. Hematol. 2012, 87(4):361-7en_GB
dc.identifier.issn1096-8652
dc.identifier.pmid22374828
dc.identifier.doi10.1002/ajh.23115
dc.identifier.urihttp://hdl.handle.net/2336/298991
dc.description.abstractMantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) are mature CD5(+) B-cell malignancies with different biological/clinical characteristics. We recently reported an association between different prognostic subgroups of CLL (i.e., IGHV mutated and unmutated) and genomic methylation pattern. However, the relationship between DNA methylation and prognostic markers, such as the proliferation gene expression signature, has not been investigated in MCL. We applied high-resolution methylation microarrays (27,578 CpG sites) to assess the global DNA methylation profiles in 20 MCL (10 each with high/low proliferation signature) and 30 CLL (15 poor-prognostic IGHV unmutated subset #1 and 15 good-prognostic IGHV mutated subset #4) samples. Notably, MCL and each CLL subset displayed distinct genomic methylation profiles. After unsupervised hierarchical clustering, 17/20 MCL cases formed a cluster separate from CLL, while CLL subsets #1 and #4 formed subclusters. Surprisingly, few differentially methylated genes (n = 6) were identified between high vs. low proliferation MCL. In contrast, distinct methylation profiles were demonstrated for MCL and CLL. Importantly, certain functional classes of genes were preferentially methylated in either disease. For instance, developmental genes, in particular homeobox transcription factor genes (e.g., HLXB9, HOXA13), were more highly methylated in MCL, whereas apoptosis-related genes were enriched among targets methylated in CLL (e.g., CYFIP2, NR4A1). Results were validated using pyrosequencing, RQ-PCR and reexpression of specific genes. In summary, the methylation profile of MCL was homogeneous and no correlation with the proliferation signature was observed. Compared to CLL, however, marked differences were discovered such as the preferential methylation of homeobox genes in MCL.
dc.language.isoenen
dc.relation.urlhttp://dx.doi.org/10.1002/ajh.23115en_GB
dc.rightsArchived with thanks to American journal of hematologyen_GB
dc.subject.meshApoptosis Regulatory Proteinsen_GB
dc.subject.meshAzacitidineen_GB
dc.subject.meshCell Divisionen_GB
dc.subject.meshCell Line, Tumoren_GB
dc.subject.meshCpG Islandsen_GB
dc.subject.meshDNA (Cytosine-5-)-Methyltransferaseen_GB
dc.subject.meshDNA Methylationen_GB
dc.subject.meshDNA, Neoplasmen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshGene Expression Regulation, Leukemicen_GB
dc.subject.meshGene Expression Regulation, Neoplasticen_GB
dc.subject.meshGenes, Homeoboxen_GB
dc.subject.meshGenes, Immunoglobulinen_GB
dc.subject.meshHistone Deacetylase Inhibitorsen_GB
dc.subject.meshHumansen_GB
dc.subject.meshHydroxamic Acidsen_GB
dc.subject.meshImmunoglobulin Heavy Chainsen_GB
dc.subject.meshLeukemia, Lymphocytic, Chronic, B-Cellen_GB
dc.subject.meshLymphoma, Mantle-Cellen_GB
dc.subject.meshMaleen_GB
dc.subject.meshNeoplasm Proteinsen_GB
dc.subject.meshSequence Analysis, DNAen_GB
dc.subject.meshTranscription Factorsen_GB
dc.titleMantle cell lymphoma displays a homogenous methylation profile: a comparative analysis with chronic lymphocytic leukemia.en
dc.typeArticleen
dc.contributor.departmentDepartment of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden.en_GB
dc.identifier.journalAmerican journal of hematologyen_GB
dc.rights.accessOpen Access - Opinn aðganguren
html.description.abstractMantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) are mature CD5(+) B-cell malignancies with different biological/clinical characteristics. We recently reported an association between different prognostic subgroups of CLL (i.e., IGHV mutated and unmutated) and genomic methylation pattern. However, the relationship between DNA methylation and prognostic markers, such as the proliferation gene expression signature, has not been investigated in MCL. We applied high-resolution methylation microarrays (27,578 CpG sites) to assess the global DNA methylation profiles in 20 MCL (10 each with high/low proliferation signature) and 30 CLL (15 poor-prognostic IGHV unmutated subset #1 and 15 good-prognostic IGHV mutated subset #4) samples. Notably, MCL and each CLL subset displayed distinct genomic methylation profiles. After unsupervised hierarchical clustering, 17/20 MCL cases formed a cluster separate from CLL, while CLL subsets #1 and #4 formed subclusters. Surprisingly, few differentially methylated genes (n = 6) were identified between high vs. low proliferation MCL. In contrast, distinct methylation profiles were demonstrated for MCL and CLL. Importantly, certain functional classes of genes were preferentially methylated in either disease. For instance, developmental genes, in particular homeobox transcription factor genes (e.g., HLXB9, HOXA13), were more highly methylated in MCL, whereas apoptosis-related genes were enriched among targets methylated in CLL (e.g., CYFIP2, NR4A1). Results were validated using pyrosequencing, RQ-PCR and reexpression of specific genes. In summary, the methylation profile of MCL was homogeneous and no correlation with the proliferation signature was observed. Compared to CLL, however, marked differences were discovered such as the preferential methylation of homeobox genes in MCL.


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