Pallarès Victor, Hoyos Montserrat, Chillón M Carmen, Barragán Eva, Prieto Conde M Isabel, Llop Marta, Falgàs Aïda, Céspedes María Virtudes, Montesinos Pau, Nomdedeu Josep F, Brunet Salut, Sanz Miguel Ángel, González-Díaz Marcos, Sierra Jorge, Mangues Ramon, Casanova Isolda
Biomedical Research Institute Sant Pau (IIB Sant Pau), Hospital de la Santa Creu i Sant Pau, Sant Antoni Maria Claret 167, Pavelló 11, 2n pis, 08025 Barcelona, Spain.
Department of Hematology, Hospital de la Santa Creu i Sant Pau, Mas Casanovas nº 90, 08041 Barcelona, Spain.
Cancers (Basel). 2018 Nov 13;10(11):436. doi: 10.3390/cancers10110436.
In recent years, several attempts have been made to identify novel prognostic markers in patients with intermediate-risk acute myeloid leukemia (IR-AML), to implement risk-adapted strategies. The non-receptor tyrosine kinases are proteins involved in regulation of cell growth, adhesion, migration and apoptosis. They associate with metastatic dissemination in solid tumors and poor prognosis. However, their role in haematological malignancies has been scarcely studied. We hypothesized that , , or could be new prognostic markers in IR-AML. We assessed , , and gene expression in a cohort of 324 patients, adults up to the age of 70, classified in the IR-AML cytogenetic group. Univariate and multivariate analyses showed that , and gene expression are independent prognostic factors in IR-AML patients. and identify a patient subgroup with good prognosis within the cohort with non-favorable FLT3/NPM1 combined mutations. In contrast, identifies a patient subgroup with poor prognosis within the worst prognosis cohort who display non-favorable FLT3/NPM1 combined mutations and underexpression of or . The combined use of these markers can refine the highly heterogeneous intermediate-risk subgroup of AML patients, and allow the development of risk-adapted post-remission chemotherapy protocols to improve their response to treatment.
近年来，人们多次尝试在中危急性髓系白血病（IR-AML）患者中识别新的预后标志物，以实施风险适应性策略。非受体酪氨酸激酶是参与细胞生长、黏附、迁移和凋亡调节的蛋白质。它们与实体瘤的转移扩散和不良预后相关。然而，它们在血液系统恶性肿瘤中的作用鲜有研究。我们推测， 、 、 或 可能是IR-AML中新的预后标志物。我们评估了324例年龄在70岁及以下的成年IR-AML细胞遗传学组患者队列中的 、 、 和 基因表达。单因素和多因素分析表明， 、 和 基因表达是IR-AML患者的独立预后因素。 和 在伴有不利FLT3/NPM1联合突变的队列中识别出预后良好的患者亚组。相反， 在预后最差的队列中识别出预后不良的患者亚组，这些患者表现出不利的FLT3/NPM1联合突变以及 或 的低表达。联合使用这些标志物可以细化AML患者高度异质性的中危亚组，并有助于制定风险适应性缓解后化疗方案，以改善他们对治疗的反应。
