p16基因缺失在成人Ph染色体阳性急性淋巴细胞白血病中的临床意义  

Clinical analysis of adult Philadelphia chromosome-positive acute iymphoblastic leukemia with p16 gene deletion

作　　者：何柏林[1] 许娜[1] 李玉玲[1] 潘成云[1] 曹睿[1] 廖立斌[1] 阴常欣[1] 蓝扬清 陆紫媛 黄继贤[1] 周红升[1] 刘启发[1] 刘晓力[1] He Bolin Xu Na Li Yuling Pan Chengyun Cao Rui Liao Libin Yin Changxin Lan Yangqing Lu Ziyuan Huang Jixian Zhou Hongsheng Liu Qifa Liu Xiaoli(Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China)

机构地区：[1]南方医科大学南方医院血液科,广州510515

出　　处：《中华血液学杂志》2017年第3期204-209,共6页Chinese Journal of Hematology

基　　金：广东省医学科研基金（2015124162336427）;南方医科大学基金（py2014n047）

摘　　要：目的探讨p16基因缺失在成人Ph染色体阳性急性淋巴细胞白血病（Ph＋ALL）中的临床意义。方法回顾性分析80例Ph＋ALL伴p16基因缺失患者的临床特征、免疫表型、细胞遗传学、分子生物学改变及其预后。结果31．3％Ph＋ALL患者合并p16基因缺失；p16基因缺失组与非缺失组相比，初诊时高白细胞计数（WBC30×10^9／L）更常见，高表达CD20，更易出现附加染色体异常，其中以累及7、8、19号染色体以及der（22）较为常见；两组诱导缓解率比较差异无统计学意义（P=0．033），p16基因缺失组患者治疗3个疗程后获BCR—ABL融合基因主要分子学反应（MMR）率和完全分子学反应（CMR）率均明显低于非缺失组（P值分别为0．034和0．036），且复发率明显高于非缺失组（P=0．033）；p16基因缺失组使用伊马替尼联合化疗者和使用达沙替尼联合化疗者的MMR、CMR率及复发率差异均无统计学意义（P值均〉0．05）；p16基因缺失组患者3年总体生存（OS）率及无病生存（DFS）率分别为37．1％和12．4％，显著低于非缺失组的54．1％和45．9％（P值分别为0．037和0．026）；25例p16基因缺失患者中14例行异基因造血干细胞移植（allo-HSCT），其中位OS时间为21个月，明显长于非移植组患者的12个月（P=0．030）。结论成人Ph’ALL伴p16基因缺失患者预后相对较差，二代酪氨酸激酶抑制剂不能明显改善其疗效，但allo-HSCT能够改善部分患者的生存，明确p16基因缺失状态对于评估预后和指导临床治疗有重要意义。Objective To investigate the clinical implications of p16 gene deletion in adult Philadelphia chromosome-positive acute lymphoblastic leukemia （Ph＋ ALL）. Methods Retrospective analysis of clinical, immunophenotypic, cytogenetics, molecular characteristics and prognosis of 80 newly diagnosed Ph＋ ALL patients with p 16 deletion. Results Of 80 adult Ph＋ ALL, the prevalence of p 16 gene deletion was 31.3%. p16 gene deletion carriers frequently accompanied with high WBC counts （WBC≥30× 10^9/L） and CD20 expression. The incidence of complex chromosome abnormality in p16 gene deletion group was higher than that in nondeletion group, with alternations in chromosome 7, 8, 19 and der （22） more frequently observed. There was no difference occurred between patients with or without p16 gene deletion in complete remission （CR） rate following induction chemotherapy combined with tyrosine kinase inhibitors （TKIs）. However, after three cycles of chemotherapy, the MMR and CMR rate in the p 16 gene deletion group was lower than patients with wild-type p16 gene （P=0.034, P=-0.036）. The p16 gene deletion patients showed no significant differences in MMR, CMR and relapse rate between Imatinib or Dasatinib plus chemotherapy （P〉 0.05）. Deletion of p16 gene was significantly associated with poor outcomes including worse overall survival （OS） （37.1% vs 54.1%, P=0.037）, lower disease free-survival （DFS） （ 12.4% vs 45.9%, P=0.026）, and increased cumulative incidence of relapse （P=0.033）. Among the 25 patients with p16 deletion, 14 underwent aIlo-HSCT and the median survival was 21 months, better than that of patients received chemotherapy alone （12 months） （P=0.030）. Conclusion This study indicated that deletion of p16 was associated with poor prognosis in adult Ph＇ ALL, and the utility of second- generation TKI （Dasatinib） does not necessarily have an edge on efficacy over Imatinib, but allo-HSCT has the potential of elongating life expectancy. It is an important signi

关 键 词：P16基因缺失 费城染色体 白血病 淋巴细胞 急性 酪氨酸激酶抑制剂 造 血干细胞移植 

分 类 号：R733.71[医药卫生—肿瘤]