杨仁池、张磊课题组在Leukemia期刊发表文章“Analysis of calreticulin mutations in Chinese patients with essential thrombocythemia: clinical implications in diagnosis, prognosis and treatment”
杨仁池、张磊团队通过对436例原发性血小板增多症(ET)患者的JAK2 V617F、MPL及新发现基因CALR的突变情况的研究,发现中国ET患者的MPL基因突变率低于欧美患者,并在ET患者中首次报道了CALR基因的获得性点突变。CALR基因突变患者的无血栓生存率显著高于JAK2 V617F突变患者。研究还发现不同的CALR基因突变亚型之间在临床特点上也存在差异。JAK2 V617F突变可以作为开始抗血小板及减低血小板治疗的分子标志,而单独存在CALR基因突变不足以成为开始药物治疗的指标。以上结果表明CALR基因突变和JAK2 V617F突变在中国ET患者的诊断、预后判断和指导治疗中有重要价值。
Recently, discovery of calreticulin (CALR) mutations fills the molecular diagnostic gap in essential thrombocythemia (ET). However, the prevalence of CALR mutations has not been reported in Asian patients, and its therapeutic implications have not yet been evaluated. We studied profiles of JAK2 V617F, MPL and CALR mutations in 436 Chinese ET patients. Compared with Caucasian patients, Chinese patients had a lower frequency of MPL mutations. We reported the first somatic point mutation in CALR in ET patients. The lower frequency of thrombosis in CALR-mutated patients was most likely due to the low thrombotic rate in type 2 CALR-mutated patients. Although no difference concerning fibrotic transformation was found between CALR-mutated and V617F+ ET, CALR-mutated patients had a higher degree of reticulin deposition. The difference was mostly ascribed to the higher rate of grade 1 reticulin deposition in type 1 CALR-mutated patients. Combination use of antiplatelet and cytoreductive agents decreased the risk of thrombosis in V617F+ patients, but not in CALR-mutated cases. We confirm the value of CALR mutations in the diagnosis and prognosis of ET in Chinese patients, and provide new evidence for making treatment strategies based on molecular markers.