Clinical impact of CD200 expression in patients with acute myeloid leukemia and correlation with other molecular prognostic factors.
Clinical impact of CD200 expression in patients with acute myeloid leukemia and correlation with other molecular prognostic factors.
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DOI：
10.18632/oncotarget.4901
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发表时间：
2015-10-06
期刊：
影响因子：
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通讯作者：
Fanin R
中科院分区：
文献类型：
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作者：
Damiani D;Tiribelli M;Raspadori D;Sirianni S;Meneghel A;Cavalllin M;Michelutti A;Toffoletti E;Geromin A;Simeone E;Bocchia M;Fanin R
CD 200是一种属于免疫球蛋白超家族的蛋白质，与淋巴组织增生性疾病和急性白血病的预后不良有关。我们研究了244例诊断为急性髓系白血病（AML）的患者的CD 200表达，以评估其对预后的影响及其与其他已知预后因素的可能相关性。CD 200阳性率为56%（136/244），其中30%（41/244）为高表达（MFI ≥ 11）。与原发性白血病相比，CD 200在继发性白血病中更常见（p = 0.0006），在CD 34阳性病例中（p = 0.00001），在Bcl 2过表达病例中（p = 0.01），在野生型Flt 3中（p = 0.004），与中间核型相比，具有有利或不利（p = 0.0003）。在单变量（p = 0.006）和多变量（p = 0.04）分析中，CD 200+患者达到完全缓解的概率低两倍。CD 200的负面影响也在总生存期中发现（p = 0.02），并且与分子的表达强度相关（p = 0.024）。CD 200对细胞遗传学不良患者的生存具有额外的负面影响（p = 0.046）和继发性白血病（p = 0.05），并且与具有有利生物标志物的患者的结果恶化相关，例如突变的NPM（p = 0.02）、野生型Flt 3（p = 0.034）、CD 34（p = 0.03）和CD 56（p = 0.03）阴性。总之，CD 200正在成为AML的预后因子和新型治疗方法的潜在靶点，旨在逆转CD 200的“不要吃我”信号或操纵由CD 200与其受体结合诱导的抑制性免疫微环境。
CD200, a protein belonging to the immunoglobulin superfamily, has been associated with a poor prognosis in lymphoproliferative disorders and in acute leukemia. We studied the expression of CD200 in a series of 244 patients with diagnosis of acute myeloid leukemia (AML), to evaluate its impact on outcome and its possible association with other known prognostic factors. CD200 was found in 136/244 (56%) patients, in 41 of whom (30%) with high intensity of expression (MFI ≥ 11). CD200 was more frequent in secondary compared to de novo leukemia (p = 0.0006), in CD34 positive cases (p = 0.00001), in Bcl2 overexpressing cases (p = 0.01), in those wild-type Flt3 (p = 0.004) and with favorable or unfavorable compared to intermediate karyotype (p = 0.0003). CD200+ patients have a two-fold lower probability to attain complete remission, both in univariate (p = 0.006) and multivariate (p = 0.04) analysis. The negative impact of CD200 was found also in overall survival (p = 0.02) and was correlated with the intensity of expression of the molecule (p = 0.024). CD200 has an additive negative impact on survival in patients with unfavorable cytogenetic (p = 0.046) and in secondary leukemia (p = 0.05), and is associate with a worsening of outcome in patients with favorable biological markers, such as mutated NPM (p = 0.02), wild-type Flt3 (p = 0.034), negativity of CD34 (p = 0.03) and of CD56 (p = 0.03). In conclusion, CD200 is emerging as both a prognostic factor and a potential target of novel therapeutic approaches for AML, aiming to reverse the “do not eat me” signal of CD200 or to manipulate the suppressive immune microenvironment induced by CD200 binding to its receptor.