JAK2 V617F genotype is a strong determinant of blast transformation in primary myelofibrosis.
JAK2 V617F genotype is a strong determinant of blast transformation in primary myelofibrosis.
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DOI：
10.1371/journal.pone.0059791
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Rosti V
中科院分区：
文献类型：
--
作者：
Barosi G;Poletto V;Massa M;Campanelli R;Villani L;Bonetti E;Viarengo G;Catarsi P;Klersy C;Rosti V
JAK 2 V617 F突变对原发性骨髓纤维化（PMF）中原始细胞转化（BT）和总生存期（OS）的影响存在争议。在一个大的患者队列中，我们应用竞争风险分析来研究JAK 2 V617 F突变对PMF中BT的影响。在462例PMF纤维化型患者（骨髓[BM]纤维化分级>0）中，我们在考克斯回归分析和BT的Fine和Gray竞争风险分析的框架内计算了BT和死亡的发生率。在考克斯回归分析中，具有野生型（wt）或纯合JAK 2 V617 F基因型是BT的因素。在竞争风险回归分析中，野生型和纯合子V617 F患者的BT风险相对于考克斯分析增加，sHR分别为2.17和2.12。校正可能影响BT的变量的结果，JAK 2 V617 F野生型和纯合子基因型仍然与BT独立相关。在133例具有PMF-纤维化前类型（BM纤维化等级= 0）的独立病例的验证队列中，包括JAK 2 V617 F基因型和老年的BT预测模型保留了高判别能力（C统计量，0.70; 95%CI，0.47至0.92）。 JAK 2 V617 F克隆中突变等位基因的积累或野生型克隆中增殖优势的选择性获得是PMF中BT的两种相关途径。这些结果对抗JAK 2药物治疗决策的影响应进行测试。
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. 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. 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). 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.
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预纤维化的骨髓纤维化沿临床和生物连续体排列的证据，具有原发性骨髓纤维化。
影响因子：
3.7
作者：
Barosi G;Rosti V;Bonetti E;Campanelli R;Carolei A;Catarsi P;Isgrò AM;Lupo L;Massa M;Poletto V;Viarengo G;Villani L;Magrini U
通讯作者：
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影响因子：
20.3
作者：
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通讯作者：
Vainchenker, William
影响因子：
20.3
作者：
Beer, Philip A.;Delhommeau, Francois;Green, Anthony R.
通讯作者：
Green, Anthony R.
DOI：
10.3324/haematol.2012.065375
发表时间：
2012-12-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Schnittger, Susanne;Bacher, Ulrike;Haferlach, Torsten
通讯作者：
Haferlach, Torsten
DOI：
10.1532/lh96.10018
发表时间：
2011-03-01
期刊：
Laboratory hematology : official publication of the International Society for Laboratory Hematology
影响因子：
--
作者：
Lopes da Silva, Rodrigo;Ribeiro, Patricia;de Sousa, Aida Botelho
通讯作者：
de Sousa, Aida Botelho