Estudios genéticos en neoplasias mieloproliferativas BCR-ABL1 negativos

Myeloproliferative neoplasms BCR-ABL1 negative (NMPs BCR-ABL1-) comprise a heterogeneous group of myeloid disorders, the most frequent are: polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (MF). Most of these pathologies are associated with mutations in JAK2 (V617F) g...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autor principal: Girardi, Natalia Soledad
Otros Autores: González, Mariana
Formato: Tesis de maestría acceptedVersion
Lenguaje:Español
Publicado: Facultad de Farmacia y Bioquímica 2016
Materias:
Neoplasias mieloproliferativas
BCR-ABL1
Patologías mieloides
Ciencia de la vida
Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_1543
http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_1543.dir/1543.PDF
Aporte de:
Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires
id I28-R145-HWA_1543
record_format dspace
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-145
collection Repositorio Digital de la Universidad de Buenos Aires (UBA)
language Español
orig_language_str_mv spa
topic Neoplasias mieloproliferativas
BCR-ABL1
Patologías mieloides
Ciencia de la vida
spellingShingle Neoplasias mieloproliferativas
BCR-ABL1
Patologías mieloides
Ciencia de la vida
Girardi, Natalia Soledad
Estudios genéticos en neoplasias mieloproliferativas BCR-ABL1 negativos
topic_facet Neoplasias mieloproliferativas
BCR-ABL1
Patologías mieloides
Ciencia de la vida
description Myeloproliferative neoplasms BCR-ABL1 negative (NMPs BCR-ABL1-) comprise a heterogeneous group of myeloid disorders, the most frequent are: polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (MF). Most of these pathologies are associated with mutations in JAK2 (V617F) gene. After the JAK2V617F mutation is acquired, a phenomenon called loss of heterozygosity (LOH) may occur. These events lead to homozygosity of the mutation, introducing the concept of allelic burden (CAL).\nIn this work were studied 41 patients including: 21 PV, 11 ET and 9 MF. The allelic burden and expression of JAK2V617F mutation were quantified by quantitative PCR (QPCR). Which allowed comparison between JAK2V617F levels in paired samples of DNA and RNA from the same patient. The average results of both measurements were in MF (mean ± ES) (62.01 ± 8.00), (80.89 ± 10.26), in PV (59.51 ± 6.01), (75.02 ± 5.48), and in TE (43.08 ± 6.49), (43.42 ± 5.95) respectively. These value showed a statistically significant correlation (Spearman r = 0.7, p <0.0001). It was noted that only 3 cases diagnosed with PV had an important rise of JAK2V617F transcripts, considered outliers, which may be associated with increased expression or overexpression of this mutation. The frequency of LOH of JAK2V617F mutation in these pathologies were: 66.6%, 57% and 27% for MF, PV and ET respectively, showing that the ET has lower incidence of JAK2V617F homozygosity. The analysis of hematological parameters (WBC count, hematocrit and platelet count) between homozygous and heterozygous patients for the JAK2V617F mutation showed significant increase in platelet count and a trend to rice in WBC in patients diagnosed with PV with homozygosity of JAK2 mutation. In MF and TE statistical differences were not observed. In this preliminary study it was observed that the JAK2V617F allelic burden would explain part of the phenotypic differences of the hematological entities included in NMPs BCR-ABL1 (-).
author2 González, Mariana
author_facet González, Mariana
Girardi, Natalia Soledad
format Tesis de maestría
Tesis de maestría
acceptedVersion
author Girardi, Natalia Soledad
author_sort Girardi, Natalia Soledad
title Estudios genéticos en neoplasias mieloproliferativas BCR-ABL1 negativos
title_short Estudios genéticos en neoplasias mieloproliferativas BCR-ABL1 negativos
title_full Estudios genéticos en neoplasias mieloproliferativas BCR-ABL1 negativos
title_fullStr Estudios genéticos en neoplasias mieloproliferativas BCR-ABL1 negativos
title_full_unstemmed Estudios genéticos en neoplasias mieloproliferativas BCR-ABL1 negativos
title_sort estudios genéticos en neoplasias mieloproliferativas bcr-abl1 negativos
publisher Facultad de Farmacia y Bioquímica
publishDate 2016
url http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_1543
http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_1543.dir/1543.PDF
work_keys_str_mv AT girardinataliasoledad estudiosgeneticosenneoplasiasmieloproliferativasbcrabl1negativos
_version_ 1766017478127779840
spelling I28-R145-HWA_15432019-09-27 Myeloproliferative neoplasms BCR-ABL1 negative (NMPs BCR-ABL1-) comprise a heterogeneous group of myeloid disorders, the most frequent are: polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (MF). Most of these pathologies are associated with mutations in JAK2 (V617F) gene. After the JAK2V617F mutation is acquired, a phenomenon called loss of heterozygosity (LOH) may occur. These events lead to homozygosity of the mutation, introducing the concept of allelic burden (CAL).\nIn this work were studied 41 patients including: 21 PV, 11 ET and 9 MF. The allelic burden and expression of JAK2V617F mutation were quantified by quantitative PCR (QPCR). Which allowed comparison between JAK2V617F levels in paired samples of DNA and RNA from the same patient. The average results of both measurements were in MF (mean ± ES) (62.01 ± 8.00), (80.89 ± 10.26), in PV (59.51 ± 6.01), (75.02 ± 5.48), and in TE (43.08 ± 6.49), (43.42 ± 5.95) respectively. These value showed a statistically significant correlation (Spearman r = 0.7, p <0.0001). It was noted that only 3 cases diagnosed with PV had an important rise of JAK2V617F transcripts, considered outliers, which may be associated with increased expression or overexpression of this mutation. The frequency of LOH of JAK2V617F mutation in these pathologies were: 66.6%, 57% and 27% for MF, PV and ET respectively, showing that the ET has lower incidence of JAK2V617F homozygosity. The analysis of hematological parameters (WBC count, hematocrit and platelet count) between homozygous and heterozygous patients for the JAK2V617F mutation showed significant increase in platelet count and a trend to rice in WBC in patients diagnosed with PV with homozygosity of JAK2 mutation. In MF and TE statistical differences were not observed. In this preliminary study it was observed that the JAK2V617F allelic burden would explain part of the phenotypic differences of the hematological entities included in NMPs BCR-ABL1 (-). Fil: Girardi, Natalia Soledad. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Buenos Aires, Argentina González, Mariana Facultad de Farmacia y Bioquímica Larripa, Irene Girardi, Natalia Soledad 2016-12-21 Las neoplasias mieloproliferativas BCR-ABL1 negativas (NMPs BCR-ABL1-) integran un grupo heterogéneo de patologías mieloides, siendo las más frecuentes la policitemia vera (PV), la trombocitemia esencial (TE) y la mielofibrosis primaria (MF). La mayoría de estas patologías se asocian con mutaciones en el gen JAK2 (V617F). Luego de adquirida la mutación JAK2V617F, puede producirse un fenómeno denominado pérdida de heterocigosidad (LOH). Estos eventos llevan a la homocigosidad de la mutación, introduciéndose el concepto de carga alélica (CAL).\nEn este trabajo se estudiaron 41 pacientes incluyendo: 21 PV, 11 TE y 9 MF, se cuantificó la carga alélica y expresión de la mutación JAK2V617F mediante PCR cuantitativa (QPCR). Lo cual permitió la comparación de los niveles de JAK2V617F en muestras pareadas de ADN y ARN del mismo paciente. Los resultados promedio obtenidos de ambas mediciones fueron en MF (media ± ES) (62,01 ± 8,00), (80,89 ± 10,26), en PV (59,51 ± 6,01), (75,02 ± 5,48) y en TE (43,08 ± 6,49), (43,42 ± 5,95) respectivamente, mostrando una correlación estadísticamente significativa (Spearman r=0,7, p<0,0001). Se observó que sólo 3 casos con diagnóstico de PV presentaban valores muy incrementados de transcriptos JAK2V617F, considerados outliers, lo cual podría asociarse a una expresión aumentada o sobreexpresión del alelo mutado. La frecuencia de LOH de la mutación JAK2V617F en MF, PV y TE fue 66,6%, 57% y 27% respectivamente, mostrando que la TE posee menor incidencia de homocigosis de dicha mutación. Se analizaron parámetros hematológicos: recuento de glóbulos blancos (WBC), plaquetas y hematocrito, en pacientes homocigotas y heterocigotas para la mutación JAK2V617F en las diferentes patologías, el análisis estadístico mostró un incremento significativo en el recuento de plaquetas y una tendencia al aumento de WBC en pacientes con PV con homocigosis de la mutación JAK2V617F. En MF y TE no se observaron diferencias. En este estudio preliminar se pudo observar que el análisis de la carga alélica de la mutación JAK2V617F podría explicar parte de las diferencias fenotípicas de las patologías incluidas en las NMPs BCR-ABL1 (-). application/pdf Carballo, Marta Cotignola, Javier Ferrer, Marcela Neoplasias mieloproliferativas BCR-ABL1 Patologías mieloides spa Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ Ciencia de la vida Estudios genéticos en neoplasias mieloproliferativas BCR-ABL1 negativos info:eu-repo/semantics/masterThesis info:ar-repo/semantics/tesis de maestría info:eu-repo/semantics/acceptedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_1543 http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_1543.dir/1543.PDF

Ejemplares similares