Helbig Grzegorz, Wozniczka Krzysztof, Wieclawek Agnieszka, Soja Anna, Bartkowska-Chrobok Aleksandra, Kyrcz-Krzemien Slawomira
Department of Haematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Poland.
Contemp Oncol (Pozn). 2014;18(4):241-5. doi: 10.5114/wo.2014.43490. Epub 2014 Aug 30.
Mutant NPM1 and CEBPA have been reported in patients with acute myeloid leukaemia (AML) and intermediate cytogenetic risk, and they appear to be associated with characteristic demographic and laboratory data, as well as clinical outcome. The objective of the study was to assess the clinical relevance of NPM1 and CEBPA mutations in AML.
This retrospective analysis was based on 60 newly diagnosed patients with AML and normal/no metaphases karyotype and known mutation status, who were treated in our centre between 2008 and 2011 according to the PALG (Polish Adult Leukaemia Group) study protocol. Pretreatment bone marrow samples were studied by G-banding analysis, and NPM1, CEBPA, and FLT3-ITD mutations were detected by polymerase chain reaction (PCR).
NPM1 mutations were detected in 21 AML patients (35%). In the NPM1-positive subgroup, the FLT3-ITD mutation was observed in 3 cases (14%), which was significantly less frequent than in the NPM1-negative patients, where FLT3-ITD was detected in 16 cases (41%; p = 0.04). Among the CEBPA-positive population (n = 11; 18%), none of the studied patients had FLT3-ITD mutation, whereas it was detected in 19 CEBPA-negative patients (0% vs. 38%; p = 0.01). The highest complete remission rate was reported for the NPM1-positive/FLT3-ITD-negative group (n = 18; 88%) and the CEBPA-positive/FLT3-ITD-negative group (n = 8; 73%). For OS, multivariable analysis revealed NPM1-positive/FLT3-ITD-negative (HR: 0.18, 95% CI: 0.19-0.63) and CEBPA-positive/FLT3-ITD-negative (HR: 0.35, 95% CI: 0.19-0.63) as favourable prognostic factors. The presence of the NPM1-negative/FLT3-ITD-positivecombination predicted adverse overall survival (HR: 2.03, 95% CI: 1.13-3.66).
NPM1 and CEBPA mutations are associated with clinical outcome in AML patients.
在急性髓系白血病（AML）及中等细胞遗传学风险患者中已报道存在NPM1和CEBPA突变，它们似乎与特征性的人口统计学和实验室数据以及临床结局相关。本研究的目的是评估AML中NPM1和CEBPA突变的临床相关性。
这项回顾性分析基于60例新诊断的AML患者，其核型为正常/无中期分裂相且已知突变状态，于2008年至2011年在我们中心按照波兰成人白血病组（PALG）研究方案接受治疗。预处理骨髓样本通过G显带分析进行研究，NPM1、CEBPA和FLT3-ITD突变通过聚合酶链反应（PCR）检测。
在21例AML患者（35%）中检测到NPM1突变。在NPM1阳性亚组中，3例（14%）观察到FLT3-ITD突变，这一频率显著低于NPM1阴性患者，后者有16例（41%）检测到FLT3-ITD突变（p = 0.04）。在CEBPA阳性人群（n = 11；18%）中，所研究的患者均未发生FLT3-ITD突变，而在19例CEBPA阴性患者中检测到该突变（0%对38%；p = 0.01）。NPM1阳性/FLT3-ITD阴性组（n = 18；88%）和CEBPA阳性/FLT3-ITD阴性组（n = 8；73%）报告的完全缓解率最高。对于总生存期（OS），多变量分析显示NPM1阳性/FLT3-ITD阴性（风险比：0.18，95%置信区间：0.19 - 0.63）和CEBPA阳性/FLT3-ITD阴性（风险比：0.35，95%置信区间：0.19 - 0.63）为有利的预后因素。NPM1阴性/FLT3-ITD阳性组合的存在预示着不良的总生存期（风险比：2.03，95%置信区间：1.13 - 3.66）。
NPM1和CEBPA突变与AML患者的临床结局相关。
