Rubio Patricia, Campos B, Digiorge J A, Gallego M S, Medina A, Rossi J G, Felice M S, Alonso C N
Department of Hematology and Oncology, Hospital de Pediatría Prof. Dr. J. P. Garrahan, Combate de los Pozos 1881, 1245, Buenos Aires, Argentina.
Department of Genetics, Hospital de Pediatría Prof. Dr. J. P. Garrahan, Buenos Aires, Argentina.
Int J Hematol. 2016 Nov;104(5):582-590. doi: 10.1007/s12185-016-2064-5. Epub 2016 Jul 19.
Mutations in NPM1, FLT3 and CEBPA genes are found in 25-35 % of adult acute myeloblastic leukemia (AML) cases and correlate with prognosis. To date, there have been no reports about these mutations in pediatric AML from Argentina. The aims of the present study were to describe the incidence of NPM1, FLT3 and CEBPA mutations and to analyze their prognostic impact in this population. The incidences of these mutations within a population of 216 pediatric AML cases were: NPM1-mutated 4.2 %, CEBPA-mutated 1.9 %, FLT3-ITD 10.2 % and FLT3-TKD 7.9 %. Among 33 patients with normal karyotype, we found significantly higher frequencies for NPM1-mutated 24.2 % and CEBPA-mutated 12.1 %. Overall survival (pOS) for the 163 eligible non-acute promyelocytic leukemia cases was 46.2 ± 4.3 %, while leukemia-free survival probability was 51.0 ± 4.4 % (n = 135). The NPM1-mutated/FLT3-ITD-negative genotype showed better outcome than any other combined NPM1/FLT3 genotype; this difference was statistically significant within the group of high-risk patients (pOS ± SE 83.3 ± 15.2 % versus 33.1 ± 4.7 %; p = 0.0251). This is the first report of the frequencies of these mutations in Argentina. Despite the limited number of patients, a favorable prognosis of AML with genotype NPM1-mutated/FLT3-ITD-negative was confirmed. This is especially relevant within the high-risk group of patients, as it may contribute to the detection of patients with better prognosis, and thus avoid unnecessary treatment intensification.
NPM1、FLT3和CEBPA基因的突变在25%-35%的成人急性髓系白血病（AML）病例中被发现，且与预后相关。迄今为止，阿根廷尚无关于小儿AML中这些突变的报道。本研究的目的是描述NPM1、FLT3和CEBPA突变的发生率，并分析它们对该人群的预后影响。在216例小儿AML病例群体中，这些突变的发生率分别为：NPM1突变4.2%，CEBPA突变1.9%，FLT3-ITD 10.2%，FLT3-TKD 7.9%。在33例核型正常的患者中，我们发现NPM1突变（24.2%）和CEBPA突变（12.1%）的频率显著更高。163例符合条件的非急性早幼粒细胞白血病病例的总生存率（pOS）为46.2±4.3%，无白血病生存率为51.0±4.4%（n = 135）。NPM1突变/FLT3-ITD阴性基因型的预后比任何其他NPM1/FLT3联合基因型都要好；在高危患者组中，这种差异具有统计学意义（pOS±SE 83.3±15.2%对33.1±4.7%；p = 0.0251）。这是阿根廷关于这些突变频率的首次报道。尽管患者数量有限，但NPM1突变/FLT3-ITD阴性基因型AML预后良好得到了证实。这在高危患者组中尤为重要，因为它可能有助于发现预后较好的患者，从而避免不必要的强化治疗。
