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...
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| Formato: | Tesis de maestría acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2016
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| 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: |
| Sumario: | 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 (-). |
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