JAK2 V617F genotype is a strong determinant of blast transformation in primary myelofibrosis.

<h4>Purpose</h4>The influence of JAK2 V617F mutation on blast transformation (BT) and overall survival (OS) in primary myelofibrosis (PMF) is controversial. In a large cohort of patients we applied competing risks analysis for studying the influence of JAK2V617F mutation on BT in PMF.<...

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Autores principales: Giovanni Barosi, Valentina Poletto, Margherita Massa, Rita Campanelli, Laura Villani, Elisa Bonetti, Gianluca Viarengo, Paolo Catarsi, Catherine Klersy, Vittorio Rosti
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:62b9e45bc5d548c6a06efc5fec3c02002021-11-18T07:51:55ZJAK2 V617F genotype is a strong determinant of blast transformation in primary myelofibrosis.1932-620310.1371/journal.pone.0059791https://doaj.org/article/62b9e45bc5d548c6a06efc5fec3c02002013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23555782/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Purpose</h4>The influence of JAK2 V617F mutation on blast transformation (BT) and overall survival (OS) in primary myelofibrosis (PMF) is controversial. In a large cohort of patients we applied competing risks analysis for studying the influence of JAK2V617F mutation on BT in PMF.<h4>Patients and methods</h4>In 462 PMF-fibrotic type patients (bone marrow [BM] fibrosis grade >0) we computed the incidence of BT and death in the framework of Cox regression analysis and of Fine and Gray competing risks analysis for BT.<h4>Results</h4>At the Cox regression analysis, having either a wild-type (wt) or a homozygous JAK2V617F genotype were factors for BT (HR, 1.98 and 2.04, respectively, with respect to the heterozygous genotype), but not for OS. At the competing risks regression analysis, the risk for BT in wt and homozygous V617F patients increased with respect to Cox analysis, giving a sHR of 2.17 and 2.12, respectively. Correcting the results for the variables that could have influence on BT, JAK2V617F wt and homozygous genotypes remained independently associated with BT. In a validation cohort of 133 independent cases with PMF-prefibrotic type (BM fibrosis grade = 0), the BT predictive model including JAK2V617F genotype and older age retained high discriminant capacity (C statistics, 0.70; 95% CI, 0.47 to 0.92).<h4>Conclusion</h4>The accumulation of mutated alleles in the JAK2V617F clone or the selective acquisition of a proliferative advantage in the wt clone are two relevant routes to BT in PMF. The influence of these results on treatment decisions with anti-JAK2 agents should be tested.Giovanni BarosiValentina PolettoMargherita MassaRita CampanelliLaura VillaniElisa BonettiGianluca ViarengoPaolo CatarsiCatherine KlersyVittorio RostiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e59791 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Giovanni Barosi
Valentina Poletto
Margherita Massa
Rita Campanelli
Laura Villani
Elisa Bonetti
Gianluca Viarengo
Paolo Catarsi
Catherine Klersy
Vittorio Rosti
JAK2 V617F genotype is a strong determinant of blast transformation in primary myelofibrosis.
description <h4>Purpose</h4>The influence of JAK2 V617F mutation on blast transformation (BT) and overall survival (OS) in primary myelofibrosis (PMF) is controversial. In a large cohort of patients we applied competing risks analysis for studying the influence of JAK2V617F mutation on BT in PMF.<h4>Patients and methods</h4>In 462 PMF-fibrotic type patients (bone marrow [BM] fibrosis grade >0) we computed the incidence of BT and death in the framework of Cox regression analysis and of Fine and Gray competing risks analysis for BT.<h4>Results</h4>At the Cox regression analysis, having either a wild-type (wt) or a homozygous JAK2V617F genotype were factors for BT (HR, 1.98 and 2.04, respectively, with respect to the heterozygous genotype), but not for OS. At the competing risks regression analysis, the risk for BT in wt and homozygous V617F patients increased with respect to Cox analysis, giving a sHR of 2.17 and 2.12, respectively. Correcting the results for the variables that could have influence on BT, JAK2V617F wt and homozygous genotypes remained independently associated with BT. In a validation cohort of 133 independent cases with PMF-prefibrotic type (BM fibrosis grade = 0), the BT predictive model including JAK2V617F genotype and older age retained high discriminant capacity (C statistics, 0.70; 95% CI, 0.47 to 0.92).<h4>Conclusion</h4>The accumulation of mutated alleles in the JAK2V617F clone or the selective acquisition of a proliferative advantage in the wt clone are two relevant routes to BT in PMF. The influence of these results on treatment decisions with anti-JAK2 agents should be tested.
format article
author Giovanni Barosi
Valentina Poletto
Margherita Massa
Rita Campanelli
Laura Villani
Elisa Bonetti
Gianluca Viarengo
Paolo Catarsi
Catherine Klersy
Vittorio Rosti
author_facet Giovanni Barosi
Valentina Poletto
Margherita Massa
Rita Campanelli
Laura Villani
Elisa Bonetti
Gianluca Viarengo
Paolo Catarsi
Catherine Klersy
Vittorio Rosti
author_sort Giovanni Barosi
title JAK2 V617F genotype is a strong determinant of blast transformation in primary myelofibrosis.
title_short JAK2 V617F genotype is a strong determinant of blast transformation in primary myelofibrosis.
title_full JAK2 V617F genotype is a strong determinant of blast transformation in primary myelofibrosis.
title_fullStr JAK2 V617F genotype is a strong determinant of blast transformation in primary myelofibrosis.
title_full_unstemmed JAK2 V617F genotype is a strong determinant of blast transformation in primary myelofibrosis.
title_sort jak2 v617f genotype is a strong determinant of blast transformation in primary myelofibrosis.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/62b9e45bc5d548c6a06efc5fec3c0200
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