Higher bone marrow LGALS3 expression is an independent unfavorable prognostic factor for overall survival in patients with acute myeloid leukemia
Higher bone marrow LGALS3 expression is an independent unfavorable prognostic factor for overall survival in patients with acute myeloid leukemia
复制标题
DOI：
10.1182/blood-2012-07-443762
复制
发表时间：
2013-04-18
期刊：
影响因子：
20.3
通讯作者：
Tien, Hwei-Fang
中科院分区：
文献类型：
--
作者：
Cheng, Chieh-Lung;Hou, Hsin-An;Tien, Hwei-Fang
半乳糖凝集素-3表达的改变常见于癌症，并可能促进肿瘤发生、癌症进展和转移。关于半乳糖凝集素-3在急性髓性白血病（AML）患者中表达的临床意义的研究很少。我们研究了编码半乳糖凝集素-3的LGALS3基因在280例原发性非急性早幼粒细胞白血病成人的骨髓（BM）单核细胞中的表达。LGALS3高表达与老年、法美英M4/M5亚型、白血病细胞CD14表达、PTPN11突变密切相关，与CEBPA突变、FLT3-ITD呈负相关。与LGALS3表达较低的患者相比，表达较高的患者完全缓解率较低，原发性难治性发生率较高，总生存期较短。该结果在一个独立的验证队列中得到了验证。将较高的LGALS3表达和其他8个危险因素（包括年龄、白细胞计数、细胞遗传学和基因突变）纳入生存分析的评分系统被证明非常有助于将AML患者分为不同的预后组（P < 0.001）。综上所述，BM LGALS3表达可作为预测AML患者临床预后的新的生物标志物，而半乳糖凝集素-3可能作为该蛋白高表达患者的潜在治疗靶点。
Alterations of galectin-3 expression are often seen in cancers and may contribute to tumorigenesis, cancer progression, and metastasis. The studies concerning clinical implications of galectin-3 expression in patients with acute myeloid leukemia (AML) are scarce. We investigated the expression of LGALS3, the gene encoding galectin-3, in the bone marrow (BM) mononuclear cells from an original cohort comprising 280 adults with primary non-acute promyelocytic leukemia. Higher LGALS3 expression was closely associated with older age, French-American-British M4/M5 subtypes, CD14 expression on leukemic cells, and PTPN11 mutation, but negatively correlated with CEBPA mutation and FLT3-ITD. Compared with patients with lower LGALS3 expression, those with higher expression had lower complete remission rates, higher primary refractory rates, and shorter overall survival. This result was validated in an independent validation cohort. A scoring system incorporating higher LGALS3 expression and 8 other risk factors, including age, white blood cell count, cytogenetics, and gene mutations, into survival analysis proved to be very useful to stratify patients with AML into different prognostic groups (P < .001). In conclusion, BM LGALS3 expression may serve as a new biomarker to predict clinical outcome in patients with AML, and galectin-3 may serve as a potential therapeutic target in those patients with higher expression of this protein.