Boissel Nicolas, Renneville Aline, Biggio Valeria, Philippe Nathalie, Thomas Xavier, Cayuela Jean-Michel, Terre Christine, Tigaud Isabelle, Castaigne Sylvie, Raffoux Emmanuel, De Botton Stephane, Fenaux Pierre, Dombret Herve, Preudhomme Claude
Service d'Hématologie Adulte, Hôpital Saint-Louis, Paris, France.
Blood. 2005 Nov 15;106(10):3618-20. doi: 10.1182/blood-2005-05-2174. Epub 2005 Jul 26.
Mutation of the nucleophosmin (NPM) gene has been reported as the most frequent mutation in acute myeloid leukemia (AML), especially in the presence of a normal karyotype. In this subgroup of intermediate-risk AML, the identification of other gene mutations (eg, FLT3, CCAAT/enhancer-binding protein-alpha [CEBPA]) has helped to refine the prognosis. This study explored the prevalence and the prognostic impact of NPM mutations in a cohort of 106 patients with normal-karyotype AML. NPM exon 12 mutations were detected by polymerase chain reaction (PCR) and fragment analysis for the insertion/deletion globally resulting in a 4-bp insertion. NPM mutations were detected in 47% of patients and were associated with a high white blood cell count, involvement of the monocytic lineage (M4/M5), and a decreased prevalence of CEBPA mutations. Complete remission rate and long-term outcome did not differ between NPM-mutated and -nonmutated patients. Prospective studies are needed to confirm the definitive place of NPM mutation detection to predict AML response to therapy.
据报道，核磷蛋白（NPM）基因突变是急性髓系白血病（AML）中最常见的突变，尤其是在核型正常的情况下。在这个中危AML亚组中，其他基因突变（如FLT3、CCAAT/增强子结合蛋白α[CEBPA]）的鉴定有助于细化预后。本研究探讨了106例核型正常的AML患者队列中NPM突变的发生率及其对预后的影响。通过聚合酶链反应（PCR）和片段分析检测NPM外显子12突变，以全面检测导致4个碱基对插入的插入/缺失情况。47%的患者检测到NPM突变，这些突变与高白细胞计数、单核细胞系受累（M4/M5）以及CEBPA突变发生率降低相关。NPM突变患者和未突变患者的完全缓解率和长期预后没有差异。需要进行前瞻性研究以确定NPM突变检测在预测AML对治疗反应中的明确地位。
