欢迎访问《中国循证儿科杂志》官方网站，今天是
English Version
中国循证儿科杂志

中国循证儿科杂志 ›› 2018, Vol. 13 ›› Issue (6): 412-416.

• 论著 • 上一篇    下一篇

MLL基因重排阳性急性淋巴细胞白血病骨髓细胞形态特征和预后的相关性

李蓓，薛天琳，崔华，巩文玉，刘曙光，李君，高超   

  1. 国家儿童医学中心，首都医科大学附属北京儿童医院血液肿瘤中心，儿童血液病与肿瘤分子分型北京市重点实验室，儿科学国家重点学科，儿科重大疾病研究教育部重点实验室 北京，100045
  • 收稿日期:2018-12-23 修回日期:2018-12-25 出版日期:2018-12-25 发布日期:2018-12-25
  • 通讯作者: 高超

Morphological characteristics and its clinical significance in children with MLL gene-rearranged acute lymphoblastic leukemia

LI Bei, XUE Tian-lin, CUI Hua, GONG Wen-yu, LIU Shu-guang, LI Jun, GAO Chao   

  1. Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics, Capital Medical University; Key Laboratory of Major Diseases in Children, Ministry of Education; Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China
  • Received:2018-12-23 Revised:2018-12-25 Online:2018-12-25 Published:2018-12-25
  • Contact: GAO Chao

PDF

1012

摘要： 目的探讨混合谱系白血病（MLL）基因重排阳性的急性淋巴细胞白血病（ALL）儿童的骨髓细胞形态特征及其与临床表现和预后的相关性。方法回顾性收集首都医科大学附属北京儿童医院（我院）血液肿瘤中心采用中国儿童白血病治疗协作组（CCLG）ALL-2008方案治疗的MLL基因重排阳性的ALL初诊患儿（MLL+组），以我院CCLGALL-2008方案治疗且时间相近、同性别的MLL阴性的初诊ALL患儿为配对条件（MLL-组）。MLL+组依据骨髓细胞中是否有嗜天青颗粒、核仁、空泡和伪足分为阳性亚组和阴性亚组。考察MLL+和MLL-组形态特征差异；比较MLL+组形态学阳性亚组和阴性亚组临床表现和无事件生存率（EFS），通过受试者工作曲线（ROC）探讨骨髓细胞不典型形态特征对患儿预后的预测能力。结果2011年1月1日至2018年5月31日共收治MLL+组26例, 其中男12例, 女14例；年龄0.4~13岁, 18例处于完全长期缓解状态，5例骨髓复发，3例确诊后放弃治疗。MLL-组30例，男16例, 女14例；年龄0.8~14岁。MLL+组骨髓细胞形态与MLL-组比较差异无统计学意义，糖原染色阳性率和赋分值均低于MLL-组。骨髓原始、幼稚淋巴细胞核仁、嗜天青颗粒、空泡、伪足的形态特征与初诊时外周血WBC、性别、年龄无相关；6例 MLL-AF4融合基因阳性者全部发现具有核仁，其他MLL重排者具有核仁的比例显著低于 MLL-AF4+者，差异有统计学意义（P=0.028）。无伪足患儿第33天MRD≥10-4的比例高于有伪足的患儿，差异有统计学意义（P=0.025），有、无核仁的患儿3年EFS［（55.0±15.0）% vs. 100%］，差异有统计学意义（P=0.049）；有、无嗜天青颗粒的患儿3年EFS［（41.7±22.2）% vs. （83.9±10.4）%］差异无统计学意义（P=0.052）;联合核仁和颗粒对MLL+组预后的ROC曲线分析结果显示，联合预测能力优于分别预测（AUC分别为0.833、0.786和0.705），P值分别为0.023、0.051和0.162。结论MLL基因重排阳性ALL患儿骨髓白血病细胞具有独特的组化染色特征，其形态表现与MLL重排亚型相关，并可预测患者预后。

Abstract: ObjectiveTo investigate the morphological characteristics of blasts in childhood acute lymphoblastic leukemia (ALL) with MLL gene rearrangement and the correlation with patients' clinical features and outcomes. MethodsThe ALL patients with MLL gene rearrangements treated on Chinese Children Leukemia Group (CCLG)-ALL 2008 protocol at Hematology and Oncology Center of Beijing Children's Hospital were enrolled retrospectively. The ALL patients without MLL gene rearrangement with the same gender to MLL+ patients enrolled at the same term were selected as controls. The MLL+ group was sub-divided into positive and negative sub groups based on the morphological characteristics in blasts. The difference of morphological characteristics between MLL+ and MLL- groups was compared; the clinical features and event-free survival (EFS) between morphological positive and negative subgroups of MLL+ patients were analyzed. Receiver operator curve (ROC) method was used to test the ability of atypical morphological features to identify the outcome of patients. ResultsA total of 26 newly diagnosed patients(12 boys and 14 girls) aging from 4 months to 13years with MLL rearrangement were enrolled between 1st Jan 2011 and 31st May 2018, whom 18 patients were in clinical remission, 5 patients suffered bone marrow relapse and 3 patients did not continue treatment after diagnosis. The control group contained 30 patients(16 boys and 14 girls) without MLL rearrangement aging from 8 months to 14 years. No significant difference of bone marrow morphology was found between ALL patients with or without MLL gene rearrangement, except for a lower percentage and integral value of glycogen staining in patients with MLL gene rearrangement. The granules, nucleoli, vacuoles and pseudopodia of bone marrow blasts were not associated with WBC, gender and age at diagnosis. Nucleoli were found in all six MLL-AF4 positive patients, significantly higher than other subtype, P=0.028. A higher proportion of high MRD (≥10-4) at day 33 was found in patients without pseudopodia, P=0.025. The prognosis of patients with nucleoli in blasts was poorer than those without, with 3-year EFS of (55.0±15.0)% for patients with nucleoli vs. 100% of those without, P=0.049. The 3-year EFS for patients with or without granules was (41.7±22.2)% vs. (83.9±10.4)% , P=0.052, which was close to cut-off of P value. ROC showed that combined analysis of nucleolus and granules features could better predict the MLL+ patients prognosis than separately, with the area under curve of 0.833, 0.786 and 0.705 respectively. ConclusionThe blasts of ALL patients'with MLL gene rearrangements have specific histochemical staining features. Their morphological features are associated with MLL rearrangement subtypes and predict the prognosis of patients.