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。