An Wenbin, Wan Yang, Guo Ye, Chen Xiaojuan, Ren Yuanyuan, Zhang Jingliao, Chang Lixian, Wei Wei, Zhang Peihong, Zhu Xiaofan
Pediatric Blood Diseases Centre, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China; State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Pediatr Blood Cancer. 2014 Dec;61(12):2256-62. doi: 10.1002/pbc.25211. Epub 2014 Aug 30.
Primary myelofibrosis (PMF) is quite rare in children. Mutations of JAK2(V617F) or MPL(W515K/L) were absent in pediatric patients with PMF according to previous studies. Recently, mutations in calreticulin (CALR) were described in adult patients with JAK2/MPL-unmutated PMF. Our study aimed to analyze the clinical and genetic features of Chinese pediatric patients with PMF.
We retrospectively investigated 14 pediatric patients diagnosed as PMF according to WHO 2008 criteria. Direct sequencing was performed for the existence of genetic alterations in JAK2, MPL, TET2, CBL, ASXL1, IDH1, IDH2, SRSF2, EZH2, DNMT3A and CALR.
In our cohort, all patients had anemia, three patients (21%) had splenomegaly, six patients (43%) had micromegakaryocytes at time of diagnosis. No patient had spontaneous remission and six patients (43%) transformed to acute myelocytic leukemia. In nine patients with evaluable cytogenetic information, three subjects (33%) had abnormal karyotypes. The median survival from time of diagnosis was 28 months. Seven patients (50%) had type 2 mutations of CALR. No patient had mutations in the other candidate genes. There was no statistical differences in age, gender, hemoglobin, WBC, neutrophil and platelet counts, percentage of circulating blast, overall survival and leukemia transformation between patients with and without CALR mutation.
Our study documented that Chinese pediatric patients with PMF in our cohort had its own clinical characteristics and poor outcome. CALR mutations were detected in 50% of our pediatric patients with PMF. Based on our study, CALR mutations screening could be used as molecular marker for diagnosis of pediatric patients with PMF.
原发性骨髓纤维化（PMF）在儿童中相当罕见。根据先前的研究，PMF患儿不存在JAK2（V617F）或MPL（W515K/L）突变。最近，在JAK2/MPL未突变的成年PMF患者中发现了钙网蛋白（CALR）突变。我们的研究旨在分析中国儿童PMF患者的临床和基因特征。
我们回顾性调查了14例根据WHO 2008标准诊断为PMF的儿科患者。对JAK2、MPL、TET2、CBL、ASXL1、IDH1、IDH2、SRSF2、EZH2、DNMT3A和CALR的基因改变进行直接测序。
在我们的队列中，所有患者均有贫血，3例患者（21%）有脾肿大，6例患者（43%）在诊断时有微小巨核细胞。无患者自发缓解，6例患者（43%）转化为急性髓细胞白血病。在9例有可评估细胞遗传学信息的患者中，3例（33%）有异常核型。从诊断时起的中位生存期为28个月。7例患者（50%）有CALR 2型突变。其他候选基因无患者发生突变。CALR突变患者与未发生CALR突变患者在年龄、性别、血红蛋白、白细胞、中性粒细胞和血小板计数、循环原始细胞百分比、总生存期和白血病转化方面无统计学差异。
我们的研究表明，我们队列中的中国儿童PMF患者有其自身的临床特征且预后较差。50%的儿童PMF患者检测到CALR突变。基于我们的研究，CALR突变筛查可作为儿童PMF患者诊断的分子标志物。
