Molecular characteristics and chromatin texture features in acute promyelocytic leukemia

dc.creatorDe Mello, MRB
dc.creatorAlbuquerque, DM
dc.creatorPereira-Cunha, FG
dc.creatorAlbanez, KB
dc.creatorPagnano, KBB
dc.creatorCosta, FF
dc.creatorMetze, K
dc.creatorLorand-Metze, I
dc.date2012
dc.date46905
dc.date2014-07-30T14:03:37Z
dc.date2015-11-26T16:44:42Z
dc.date2014-07-30T14:03:37Z
dc.date2015-11-26T16:44:42Z
dc.date.accessioned2018-03-28T23:30:07Z
dc.date.available2018-03-28T23:30:07Z
dc.identifierDiagnostic Pathology. Biomed Central Ltd, v. 7, 2012.
dc.identifier1746-1596
dc.identifierWOS:000310291400001
dc.identifier10.1186/1746-1596-7-75
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/57731
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/57731
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1274008
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionBackground: Acute promyelocytic leukemia is a cytogenetically well defined entity. Nevertheless, some features observed at diagnosis are related to a worse outcome of the patients. Methods: In a prospective study, we analyzed peripheral (PB) leukocyte count, immunophenotype, methylation status of CDKN2B, CDKN2A and TP73; FLT3 and NPM1 mutations besides nuclear chromatin texture characteristics of the leukemic cells. We also examined the relation of these features with patient's outcome. Results: Among 19 cases, 4 had a microgranular morphology, 7 presented PB leukocytes >10x10(9)/l, 2 had FLT3-ITD and 3 had FLT3-TKD (all three presenting a methylated CDKN2B). NPM1 mutation was not observed. PB leukocyte count showed an inverse relation with standard deviation of gray levels, contrast, cluster prominence, and chromatin fractal dimension (FD). Cases with FLT3-ITD presented a microgranular morphology, PB leukocytosis and expression of HLA-DR, CD34 and CD11b. Concerning nuclear chromatin texture variables, these cases had a lower entropy, contrast, cluster prominence and FD, but higher local homogeneity, and R(2)45, in keeping with more homogeneously distributed chromatin. In the univariate Cox analysis, a higher leukocyte count, FLT3-ITD mutation, microgranular morphology, methylation of CDKN2B, besides a higher local homogeneity of nuclear chromatin, a lower chromatin entropy and FD were associated to a worse outcome. All these features lost significance when the cases were stratified for FLT3-ITD mutation. Methylation status of CDNK2A and TP73 showed no relation to patient's survival. Conclusion: in APL, patients with FLT3-ITD mutation show different clinical characteristics and have blasts with a more homogeneous chromatin texture. Texture analysis demonstrated that FLTD-ITD was accompanied not only by different cytoplasmic features, but also by a change in chromatin structure in routine cytologic preparations. Yet we were not able to detect chromatin changes by nuclear texture analysis of patients with the FTLD-TKD or methylation of specific genes.
dc.description7
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFAPESP [2007/54686-0]
dc.descriptionCNPq [302277/2009-9, 307270/2010-6, 402022/2010-6]
dc.languageen
dc.publisherBiomed Central Ltd
dc.publisherLondon
dc.publisherInglaterra
dc.relationDiagnostic Pathology
dc.relationDiagn. Pathol.
dc.rightsaberto
dc.sourceWeb of Science
dc.subjectPromyelocytic leukemia
dc.subjectPrognosis
dc.subjectFLT3-ITD
dc.subjectChromatin texture
dc.subjectNucleolar Organizer Regions
dc.subjectFractal Dimension
dc.subjectPromoter Methylation
dc.subjectNuclear Chromatin
dc.subjectPrognostic-factor
dc.subjectLymphoblastic-leukemia
dc.subjectMyeloid-leukemia
dc.subjectCancer
dc.subjectFlt3
dc.subjectEpigenetics
dc.titleMolecular characteristics and chromatin texture features in acute promyelocytic leukemia
dc.typeArtículos de revistas


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