Distribution and levels of cell surface expression of CD33 and CD123 in acute myeloid leukemia.
Distribution and levels of cell surface expression of CD33 and CD123 in acute myeloid leukemia.
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DOI：
10.1038/bcj.2014.39
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发表时间：
2014-06-13
影响因子：
12.8
通讯作者：
Oelschlaegel, U.
中科院分区：
文献类型：
--
作者：
Ehninger, A.;Kramer, M.;Roellig, C.;Thiede, C.;Bornhaeuser, M.;von Bonin, M.;Wermke, M.;Feldmann, A.;Bachmann, M.;Ehninger, G.;Oelschlaegel, U.
由于抗CD 33免疫毒素gemtuzumab ozogamicin最近的阳性结果，靶向CD 33的急性髓性白血病（AML）治疗有许多希望。在此，通过流式细胞术研究了319例患者的AML原始细胞上的CD 33和CD 123表达，并提供了法国-美国-英国/世界卫生组织（FAB/WHO）分类、细胞遗传学和分子畸变的详细信息。87.8%的AML表达CD 33，因此可以用抗CD 33疗法靶向治疗。此外，9.4%的AML表达CD 123，而不伴随CD 33表达。因此，几乎所有AML都可以通过CD 33或CD 123靶向。在69.5%的患者中观察到两种抗原同时存在。最重要的是，即使是细胞遗传学不良的AML，其表达的CD 33和CD 123水平也与有利和中间亚型的AML相当。一些具有不利改变的患者组，例如FMS相关酪氨酸激酶3-内部串联重复（FLT 3-ITD）突变、高FLT 3-ITD突变体/野生型比率和5号单体性，甚至以CD 33和CD 123的高表达为特征。此外，突变型核磷蛋白（NPM 1）患者的原始细胞显示出显著更高的CD 33和CD 123表达，这表明在突变型NPM 1阳性AML中进行最小残留疾病指导干预的可能性。这些结果刺激了使用双特异性抗体或表达嵌合抗原受体的工程化T细胞将免疫效应细胞重定向至表达CD 33和CD 123的母细胞的新概念的发展。
Owing to the more recent positive results with the anti-CD33 immunotoxin gemtuzumab ozogamicin, therapy against acute myeloid leukemias (AMLs) targeting CD33 holds many promises. Here, CD33 and CD123 expression on AML blasts was studied by flow cytometry in a cohort of 319 patients with detailed information on French–American–British/World Health Organization (FAB/WHO) classification, cytogenetics and molecular aberrations. AMLs of 87.8% express CD33 and would therefore be targetable with anti-CD33 therapies. Additionally, 9.4% of AMLs express CD123 without concomitant CD33 expression. Thus, nearly all AMLs could be either targeted via CD33 or CD123. Simultaneous presence of both antigens was observed in 69.5% of patients. Most importantly, even AMLs with adverse cytogenetics express CD33 and CD123 levels comparable to those with favorable and intermediate subtypes. Some patient groups with unfavorable alterations, such as FMS-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations, high FLT3-ITD mutant/wild-type ratios and monosomy 5 are even characterized by high expression of CD33 and CD123. In addition, blasts of patients with mutant nucleophosmin (NPM1) revealed significantly higher CD33 and CD123 expression pointing toward the possibility of minimal residual disease-guided interventions in mutated NPM1-positive AMLs. These results stimulate the development of novel concepts to redirect immune effector cells toward CD33- and CD123-expressing blasts using bi-specific antibodies or engineered T cells expressing chimeric antigen receptors.
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DOI：
10.3324/haematol.2011.043786
发表时间：
2011-10-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
De Propris, Maria Stefania;Raponi, Sara;Guarini, Anna
通讯作者：
Guarini, Anna
影响因子：
82.9
作者：
Eppert, Kolja;Takenaka, Katsuto;Dick, John E.
通讯作者：
Dick, John E.
DOI：
10.1111/j.1365-2362.2007.01746.x
发表时间：
2007-01-01
影响因子：
5.5
作者：
Hauswirth, A. W.;Florian, S.;Valent, P.
通讯作者：
Valent, P.
影响因子：
20.3
作者：
Kottaridis, PD;Gale, RE;Linch, DC
通讯作者：
Linch, DC
影响因子：
3.5
作者：
Hwang, Keumrock;Park, Chan-Jeoung;Seo, Jong-Jin
通讯作者：
Seo, Jong-Jin