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dc.contributor.authorPaes, Jhemerson Fernandes-
dc.date.available2023-11-08-
dc.date.available2023-11-21T13:03:19Z-
dc.date.issued2023-07-29-
dc.identifier.urihttp://repositorioinstitucional.uea.edu.br//handle/riuea/5341-
dc.description.abstractBCR::ABL1 negative myeloproliferative neoplasms are hematological disorders characterized by hyperplasia of myeloid elements. Essential thrombocythemia, polycythemia vera, and myelofibrosis are the most frequent diseases within this group and can be differentiated by clinical, laboratory, and genetic findings. JAK2V617F is a common genetic alteration in BCR::ABL1- negative myeloproliferative neoplasms and is associated with the 46/1 haplotype, where the rs10974944 (C>G) variant is located in intron 12 of the JAK2 gene and serves as a genetic marker for this haplotype. This haplotype also influences laboratory alterations, allelic frequency of the variants, and correlations with familial myeloproliferative neoplasms. The promoter region also plays a role in the modulation within the etiopathogenic scenario of other neoplasms; however, little is still known about the action of variants in this gene segment in myeloproliferative diseases. Objective: To evaluate the presence of the 46/1 haplotype and the promoter region of the JAK2 gene. Methodology: The study included 108 individuals clinically diagnosed with polycythemia vera (n=39), essential thrombocythemia (n=61), and myelofibrosis (n=8). Clinical, laboratory, and molecular analyses using polymerase chain reaction and Sanger sequencing were important for obtaining the data. Results: In intron 12, in addition to rs10974944 (C>G), the variants rs10119004 (A>G), rs1081515 (G>T), and rs59720809 (A>G) were identified. Individuals with polycythemia vera and carriers of the rs10974944 G allele showed significantly increased mean corpuscular volume and mean corpuscular hemoglobin values (p < 0.05). On the other hand, the essential thrombocythemia group showed elevated levels of red blood cells, hematocrit, and hemoglobin (p < 0.05). An association was observed between the genotypic frequency of rs10974944 (G) and the status of the JAK2V617F variant. Individuals with the G allele and the GG genotype of rs10974944 showed a significant association with a positive status for JAK2V617F (p < 0.05), as well as an increased allelic frequency of the variant. Furthermore, rs10815151 showed an association with a negative status for JAK2V617F. In the promoter region, the variants rs6476933 (C>T), rs189703877 (A>C), rs73389454 (A>C), rs1887428 (G>C), and rs1887429 (G>T) were identified. The G allele of rs1887428 was more frequent in JAK2V617F-positive patients with a VAF≥50%, while the variant allele (C) showed an inverse relationship. rs6476933 (C>T), rs1887428 (G>C), and rs1887429 (G>T) apparently create transcription factor binding sites. Conclusion: rs10974944 (G) was found to be associated with a positive status for JAK2V617F, as well as laboratory alterations and an increase in the allelic frequency of the variant, while rs10815151 was shown to be a protective factor against JAK2V617F in the studied population. Additionally, rs1887428 likely plays a role in the regulation of JAK2, where the creation of a transcription factor binding site alters the gene expression.pt_BR
dc.languageporpt_BR
dc.publisherUniversidade do Estado do Amazonaspt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectJanus quinasept_BR
dc.subjectNeoplasia mieloproliferativapt_BR
dc.subjectHaplótipopt_BR
dc.subjectvariação genéticapt_BR
dc.subjectMyeloproliferative neoplasmpt_BR
dc.titleEstudo do haplótipo 46/1 e promotor do gene JAK2 em pacientes com neoplasias mieloproliferativas BCR:: ABL 1 negativas atendidos na Fundação Hospitalar de Hematologia e Hemoterapia do Amazonaspt_BR
dc.title.alternativeStudy of the 46-1 haplotype and promoter of the JAK2 gene in patients with BCR ABL 1 negative myeloproliferative neoplasms treated at the Fundação Hospitalar de Hematologia e Hemoterapia do Amazonaspt_BR
dc.typeDissertaçãopt_BR
dc.date.accessioned2023-11-21T13:03:19Z-
dc.contributor.advisor-co1Tarragô, Andréa Monteiro-
dc.contributor.advisor-co1Latteshttp://lattes.cnpq.br/4644326589690231pt_BR
dc.contributor.advisor1Mourão, Lucivana Prata de Souza-
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/1135734404648095pt_BR
dc.contributor.referee1Mourão, Lucivana Prata de Souza-
dc.contributor.referee1Latteshttp://lattes.cnpq.br/1135734404648095pt_BR
dc.contributor.referee2Santos, Maria da Conceição Freitas dos-
dc.contributor.referee2Latteshttp://lattes.cnpq.br/7618353060771291pt_BR
dc.contributor.referee3Sadahiro, Aya-
dc.contributor.referee3Latteshttp://lattes.cnpq.br/8658798733544812pt_BR
dc.creator.Latteshttp://lattes.cnpq.br/4827067663630750pt_BR
dc.description.resumoNeoplasias mieloproliferativas BCR::ABL1 negativas são doenças hematológicas caracterizadas por hiperplasia dos elementos mieloides. Trombocitemia essencial, policitemia vera e mielofibrose são as mais frequentes dentro desse grupo de doenças e podem ser diferenciadas por achados clínicos, laboratoriais e genéticos. JAK2V617F é uma alteração genética comum em neoplasias mieloproliferativas BCR::ABL1 negativas e está associado ao haplótipo 46/1, onde localiza-se rs10974944 (C>G), variante localizada no íntron 12 do gene JAK2 e marcador genético deste haplótipo. Esse haplótipo também influencia as alterações laboratoriais, frequência alélica das variantes e correlações com neoplasias mieloproliferativas familiares. A região promotora também exerce papel na modulação dentro do cenário etiopatogênico de outras neoplasias, todavia, nas mieloproliferativas ainda pouco se conhece sobre a ação de variantes nessa porção gênica. Objetivo: avaliar a presença do haplótipo 46/1 e a região promotora do gene JAK2. Metodologia: foram incluídos no estudo 108 indivíduos diagnosticados clinicamente com policitemia vera (n=39), trombocitemia essencial (n=61) e mielofibrose (n=8). Dados clínicos, laboratoriais e análises moleculares por reação em cadeia da polimerase e sequenciamento de Sanger foram importantes para obtenção dos dados. Resultados: No íntron 12 foram identificadas, além de rs10974944 (C>G), as variantes rs10119004 (A>G), rs1081515 (G>T) e rs59720809 (A>G). Indivíduos com policitemia vera e portadores do alelo G de rs10974944 apresentaram valores significativamente aumentados de volume corpuscular médio e hemoglobina corpuscular média (p < 0,05). Por outro lado, no grupo de trombocitemia essencial, foram observados níveis elevados de glóbulos vermelhos, hematócrito e hemoglobina (p < 0,05). Foi observada uma associação entre a frequência genotípica de rs10974944 (G) e o status da variante JAK2V617F. Indivíduos com o alelo G e o genótipo GG de rs10974944 apresentaram uma associação significativa com o status positivo para JAK2V617F (p < 0,05), assim como um aumento na frequência alélica da variante. Além disso, rs10815151 demonstrou uma associação com o status negativo para JAK2V617F. Na região promotora foram identificadas rs6476933 (C>T), rs189703877 (A>C), rs73389454 (A>C), rs1887428 (G>C) e rs1887429 (G>T). O alelo G de rs1887428 demonstrou-se mais frequente em pacientes JAK2V617F positivo VAF≥50%, ao passo que o alelo variante (C) apresentou relação inversa. rs6476933 (C>T), rs1887428 (G>C) rs1887429 (G>T) aparentemente criam sítios de fatores de transcrição. Conclusão: rs10974944 (G) demonstrou-se associada ao status positivo para JAK2V617F, bem como alterações laboratoriais e um aumento na frequência alélica da variante ao passo que rs10815151 demonstrou-se como um fator protetor a JAK2V617F na população estudada. Já rs1887428 apresentou provável papel na regulação de JAK2, onde a criação de sítio de fatores de transcrição altera a expressão do genept_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.programPPGH -PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIApt_BR
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