Cabrera Maria Elena, Monardes Virginia, Salgado Carmen, Cares Carolina, Gonzalez Claudio
Hospital del Salvador, Universidad de Chile, Santiago, Chile.
Hospital del Salvador, Universidad de Chile, Santiago, Chile.
Hematol Transfus Cell Ther. 2023 Jan-Mar;45(1):77-82. doi: 10.1016/j.htct.2021.06.003. Epub 2021 Jul 30.
Acute myeloid leukemia (AML) is a heterogeneous disease and approximately one-third of its carriers do not have evident genetic abnormalities. The mutation of specific molecular markers, such as fms-like tyrosine kinase 3 (FTL3) internal tandem duplication (ITD), FLT3 tyrosine kinase domain (TKD) and nucleophosmin (NPM1), are associated with an adverse and favorable prognosis, respectively.
The objective was to determine the prevalence of FLT3/ITD and NPM1 in Chilean patients and their association with clinical data and prognosis.
Two hundred and thirty-two children were studied between 2011 and 2017, the median being 8.6 years (ranging from 1 to 18 months). Acute promyelocytic leukemia (APL) was diagnosed in 29%. The FLT3/ITD-mutated in non-promyelocytic AML was at 10% (14/133) and the FLT3/TKD, at 3.7% (2/54). In APL, it was at 25.4% (16/63). In non-promyelocytic AML, the FLT3/ITD-mutated was associated with a high leucocyte count, the median being 28.5 x mm (n = 14) versus 19.4 x mm (n = 119), (p = 0.25), in non-mutated cases. In APL, the median was 33.6 x mm3 (n = 15) versus 2.8 x mm3 (n = 47), (p < 0.001). The five-year overall survival (OS) in non-promyelocytic AML with non-mutated and mutated FLT3/ITD were 62.7% and 21.4%, respectively, (p < 0.001); the 5-year event-free survival (EFS) were 79.5% and 50%, respectively, (p < 0.01). The five-year OS in APL with non-mutated and mutated FLT3/ITD was 84.7% and 62.5%, respectively, (p = 0.05); the 5-year EFS was 84.7% and 68.8%, respectively, (p = 0.122). The NPM1 mutation was observed in 3.2% (5/155), all non-promyelocytic AML with the normal karyotype.
The FLT3/ITD mutation was observed more frequently in APL and associated with a higher white cell count at diagnosis. However, the most important finding was that the FLT3/ITD mutation was associated with a shorter survival in non-promyelocytic AML.
急性髓系白血病（AML）是一种异质性疾病，约三分之一的患者没有明显的基因异常。特定分子标志物的突变，如FMS样酪氨酸激酶3（FLT3）内部串联重复（ITD）、FLT3酪氨酸激酶结构域（TKD）和核磷蛋白（NPM1），分别与不良预后和良好预后相关。
确定智利患者中FLT3/ITD和NPM1的患病率及其与临床数据和预后的关联。
2011年至2017年期间对232名儿童进行了研究，中位年龄为8.6岁（范围为1至18个月）。29%的患者被诊断为急性早幼粒细胞白血病（APL）。非早幼粒细胞AML中FLT3/ITD突变率为10%（14/133），FLT3/TKD突变率为3.7%（2/54）。在APL中，该突变率为25.4%（16/63）。在非早幼粒细胞AML中，FLT3/ITD突变与高白细胞计数相关，突变病例的中位数为28.5×10⁹/mm³（n = 14），而非突变病例为19.4×10⁹/mm³（n = 119），（p = 0.25）。在APL中，中位数分别为33.6×10⁹/mm³（n = 15）和2.8×10⁹/mm³（n = 47），（p < 0.001）。非早幼粒细胞AML中FLT3/ITD未突变和突变的患者5年总生存率（OS）分别为62.7%和21.4%，（p < 0.001）；5年无事件生存率（EFS）分别为79.5%和50%，（p < 0.01）。APL中FLT3/ITD未突变和突变的患者5年OS分别为84.7%和62.5%，（p = 0.05）；5年EFS分别为84.7%和68.8%，（p = 0.122）。在3.2%（5/155）的患者中观察到NPM1突变，所有病例均为核型正常的非早幼粒细胞AML。
FLT3/ITD突变在APL中更常见，且与诊断时较高的白细胞计数相关。然而，最重要的发现是FLT3/ITD突变与非早幼粒细胞AML患者的生存期缩短有关。
