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Sequential mutational evaluation of CALR -mutated myeloproliferative neoplasms with thrombocytosis reveals an association between CALR allele burden evolution and disease progression.
British Journal of Haematology ( IF 5.1 ) Pub Date : 2019-11-11 , DOI: 10.1111/bjh.16276
Laurane Cottin 1, 2, 3, 4 , Jérémie Riou 5 , Corentin Orvain 1, 2, 4, 6 , Jean Christophe Ianotto 4, 7 , Françoise Boyer 4, 6 , Maxime Renard 1, 3, 4 , Matgorzata Truchan-Graczyk 8 , Anne Murati 9 , Rébecca Jouanneau-Courville 3 , Olivier Allangba 10 , Olivier Mansier 11, 12, 13 , Barbara Burroni 14 , Marie-Christine Rousselet 2, 15 , Isabelle Quintin-Roué 16 , Antoine Martin 17 , Sophie Sadot-Lebouvier 18 , Yves Delneste 1, 4, 19 , Jean-Marie Chrétien 20 , Mathilde Hunault-Berger 1, 2, 4, 6 , Odile Blanchet 1, 2, 3, 4, 21 , Eric Lippert 4, 22, 23 , Valérie Ugo 1, 2, 3, 4 , Damien Luque Paz 1, 2, 3, 4
Affiliation  

In myeloproliferative neoplasms (MPN), JAK2V617F allele burden measurement has an impact on prognosis that helps in patient monitoring. Less is known about its usefulness in CALR-mutated cases. Additional mutations found by next-generation sequencing have also shown an impact on prognosis that may drive therapeutic choices, especially in myelofibrosis, but few studies focused on CALR-mutated patients. We performed a molecular evaluation combining next-generation sequencing with a myeloid panel and CALR allele burden measurement at diagnosis and during follow-up in a cohort of 45 patients with CALR-mutated essential thrombocythaemia. The bone marrow histology was also blindly reviewed in order to apply the WHO2016 classification. The most frequently mutated gene was TET2 (11/21 mutations). CALR type 1-like patients appear to have a more complex molecular landscape. We found an association between disease progression and CALR allele burden increase during follow-up, independently of additional mutations and WHO2016-reviewed diagnosis. Patients with disease progression at the time of follow-up showed a significant increase in CALR allele burden (+16·7%, P = 0·005) whereas patients without disease progression had a stable allele burden (+3·7%, P = 0·194). This result argues for clinical interest in CALR allele burden monitoring.

中文翻译:

对伴有血小板增多症的CALR突变的骨髓增生性肿瘤进行顺序突变评估,发现CALR等位基因负荷发展与疾病进展之间存在关联。

在骨髓增生性肿瘤(MPN)中,JAK2V617F等位基因负荷测量对预后有影响,有助于患者监测。人们对它在CALR突变病例中的有用性知之甚少。下一代测序发现的其他突变也显示出对预后的影响,可能会推动治疗选择,尤其是在骨髓纤维化中,但很少有研究关注CALR突变的患者。我们对45名CALR突变型原发性血小板增多症患者进行诊断和随访期间,结合了新一代测序与髓样面板和CALR等位基因负荷测量相结合的分子评估。还盲目检查了骨髓组织学,以应用WHO2016分类。突变频率最高的基因是TET2(11/21突变)。类似于CALR 1型的患者似乎具有更复杂的分子态势。我们发现随访期间疾病进展与CALR等位基因负荷增加之间存在关联,与其他突变和WHO2016审查的诊断无关。随访时有疾病进展的患者显示CALR等位基因负担显着增加(+ 16·7%,P = 0·005),而无疾病进展的患者则有稳定的等位基因负担(+ 3·7%,P = 0·194)。该结果证明了对CALR等位基因负荷监测的临床兴趣。P = 0·005),而没有疾病进展的患者具有稳定的等位基因负担(+ 3·7%,P = 0.194)。该结果证明了对CALR等位基因负荷监测的临床兴趣。P = 0·005),而没有疾病进展的患者具有稳定的等位基因负担(+ 3·7%,P = 0.194)。该结果证明了对CALR等位基因负荷监测的临床兴趣。
更新日期:2019-11-13
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