The incidence and clinical significance of nucleophosmin mutations in childhood AML
The incidence and clinical significance of nucleophosmin mutations in childhood AML
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DOI：
10.1182/blood-2007-02-076604
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发表时间：
2007-08-01
期刊：
影响因子：
20.3
通讯作者：
Small, Donald
中科院分区：
文献类型：
--
作者：
Brown, Patrick;McIntyre, Emily;Small, Donald
核磷蛋白基因 (NPM1) 外显子 12 的移码突变导致 NPM 蛋白 (NPMc(+)) 细胞质定位异常，并发生在 25% 至 35% 的成人急性髓系白血病 (AML) 中。在患有 AML 的成人中，NPMc(+) 与正常核型、FLT3/ITD 突变、高缓解诱导率和改善的生存率相关（特别是在缺乏 FLT3/ITD 的患者中）。 NPMc(+) 在儿童 AML 中的特征尚未得到很好的表征。本研究探讨了在一项大型合作组临床试验 (POG-9421) 中接受治疗的 295 名新诊断 AML 儿童中 NPMc(+) 的发生率和临床意义。我们发现 NPMc(+) 在儿童 AML 中相对罕见（295 名患者中的 23 名，8%）；并且与 FLT3/ITD 突变 (P = .046)、女性 (P = .029)、老年 (P = .047) 和正常细胞遗传学 (P < .001) 显着相关。 NPMc(+) 对缺乏 FLT3/ITD 的儿童的生存具有有利影响（5 年 EFS，69% vs 35%；风险比，0.39；P = .051），其程度与 t(8;21) 和 inv(16) 的有利影响相似。我们的结论是，NPMc(+) 在儿童 AML 中相对罕见，特别是在年幼的儿童中。 NPMc(+) 并不能消除 FLT3/ITD 突变的负面预后影响，但可能有助于通过识别预后较好的组来对缺乏 FLT3/ITD 突变的儿童进行风险分层。
Frameshift mutations in exon 12 of the nucleophosmin gene (NPM1) result in aberrant cytoplasmic localization of the NPM protein (NPMc(+)) and occur in 25% to 35% of adult acute myeloid leukemia (AML). In adults with AML, NPMc(+) has been associated with normal karyotype, FLT3/ITD mutations, high remission induction rates, and improved survival (particularly in patients lacking FLT3/ITD). NPMc(+) has not been well characterized in childhood AML. This study examines the incidence and clinical significance of NPMc(+) in 295 children with newly diagnosed AML treated on a large cooperative group clinical trial (POG-9421). We find that NPMc(+) is relatively uncommon in childhood AML (23 of 295 patients, 8%); and is significantly associated with FLT3/ITD mutations (P = .046), female sex (P = .029), older age (P = .047), and normal cytogenetics (P < .001). There is a favorable impact of NPMc(+) on survival in children lacking FLT3/ITD (5-year EFS, 69% vs 35%; hazard ratio, 0.39; P = .051), which is similar in magnitude to the favorable impact of t(8;21) and inv(16). We conclude that NPMc(+) is relatively rare in childhood AML, particularly in younger children. NPMc(+) does not abrogate the negative prognostic influence of FLT3/ITD mutations, but may contribute to risk stratification in children who lack FLT3/ITD mutations by identifying a group with superior prognosis.