Hematological malignancies possess a distinctive immunologic microenvironment compared with solid tumors. Here, using an established computational algorithm (CIBERSORT), we systematically analyzed the overall distribution of 22 tumor-infiltrating leukocyte (TIL) populations in more than 2000 bone marrow (BM) samples from 5 major hematological malignancies and healthy controls. Focusing on significantly altered TILs in acute myeloid leukemia (AML), we found that patients with AML exhibited increased frequencies of M2 macrophages, compared to either healthy controls or the other four malignancies. High infiltration of M2 macrophages was associated with poor outcome in AML. Further analysis revealed that CD206, a M2 marker gene, could faithfully reflect variation in M2 fractions and was more highly expressed in AML than normal controls. High CD206 expression predicted inferior overall survival (OS) and event-free survival (EFS) in two independent AML cohorts. Among 175 patients with intermediate-risk cytogenetics, the survival still differed greatly between low and high CD206 expressers (OS; P < .0001; 3-year rates, 56% v 32%; EFS; P < .001; 3-year rates, 47% v 25%). When analyzed in a meta-analysis, CD206 as a continuous variable showed superior predictive performance than classical prognosticators in AML (BAALC, ERG, EVI1, MN1, and WT1). In summary, M2 macrophages are preferentially enriched in AML. The M2 marker CD206 may serve as a new prognostic marker in AML.

中文翻译：

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M2巨噬细胞标记CD206：急性髓细胞白血病的一种新的预后指标。

与实体瘤相比，血液恶性肿瘤具有独特的免疫微环境。在这里，我们使用已建立的计算算法（CIBERSORT），系统地分析了来自5个主要血液系统恶性肿瘤和健康对照的2000多个骨髓（BM）样本中22种肿瘤浸润白细胞（TIL）群体的总体分布。着眼于急性髓细胞性白血病（AML）中TIL的显着改变，我们发现与健康对照组或其他四个恶性肿瘤相比，AML患者的M2巨噬细胞发生率增加。M2巨噬细胞的高浸润与AML不良预后相关。进一步的分析表明，M2标记基因CD206可以忠实地反映M2片段的变化，并且在AML中比正常对照组表达更高。高CD206表达可预测两个独立的AML队列的总体生存期（OS）和无事件生存期（EFS）。在175位中危细胞遗传学患者中，CD206低表达和高表达之间的生存率仍存在很大差异（OS； P <.0001； 3年率，56％vs 32％； EFS； P <.001； 3年率，47％对25％）。当在荟萃分析中分析时，作为连续变量的CD206在AML（BAALC，ERG，EVI1，MN1和WT1）中表现出比经典预后更好的预测性能。总之，M2巨噬细胞优先富含AML。M2标记CD206可以作为AML中的新预后标记。高和低CD206表达者之间的生存率仍存在很大差异（OS； P <.0001； 3年率，56％对32％； EFS； P <.001； 3年率，47％对25％）。当在荟萃分析中分析时，作为连续变量的CD206在AML（BAALC，ERG，EVI1，MN1和WT1）中表现出比经典预后更好的预测性能。总之，M2巨噬细胞优先富含AML。M2标记CD206可以作为AML中的新预后标记。高和低CD206表达者之间的生存率仍存在很大差异（OS； P <.0001； 3年率，56％对32％； EFS； P <.001； 3年率，47％对25％）。当在荟萃分析中分析时，作为连续变量的CD206在AML（BAALC，ERG，EVI1，MN1和WT1）中表现出比经典预后更好的预测性能。总之，M2巨噬细胞优先富含AML。M2标记CD206可以作为AML中的新预后标记。