Expression of the target receptor CD33 in CD34+/CD38-/CD123+ AML stem cells
Expression of the target receptor CD33 in CD34+/CD38-/CD123+ AML stem cells
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DOI：
10.1111/j.1365-2362.2007.01746.x
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发表时间：
2007-01-01
影响因子：
5.5
通讯作者：
Valent, P.
中科院分区：
文献类型：
--
作者：
Hauswirth, A. W.;Florian, S.;Valent, P.
背景：CD 33（Siglec-3）作为急性髓性白血病（AML）抗体介导治疗的靶点变得越来越重要。在正常骨髓生成中，CD 33的表达仅限于分化的晚期阶段，而原始干细胞不表达CD 33。材料与方法：采用多色染色技术，对11例AML患者的白血病干细胞进行检测，确定白血病干细胞为CD 34（+）/CD 38（-）/CD 123（+）细胞。AML干细胞纯化细胞分选和CD 33 mRNA的表达进行了检查，通过逆转录-聚合酶链反应（RT-PCR）。结果：在所有患者中，其中大部分的成髓细胞表达CD 33（n = 8），AML祖细胞与CD 33抗体P67.6。利用受辐射的NOD/SCID小鼠进行的再增殖实验证实，这些患者的AML干细胞存在于白血病克隆的CD 33（+）亚群中。此外，在RT-PCR分析中发现，来自CD 33（+）AML患者的高度纯化的AML干细胞（纯度> 98%）表达CD 33 mRNA。正常骨髓CD 34（+）/CD 38（-）细胞和CD 33阴性AML患者的白血病干细胞均未检测到CD 33。这一观察结果有利于在AML中采用CD 33靶向抗体的新治疗概念。
Background: CD33 (Siglec-3) is becoming increasingly important as a target of antibody-mediated therapy in acute myeloid leukaemia (AML). In normal myelopoiesis, expression of CD33 is restricted to advanced stages of differentiation, whereas primitive stem cells do not express CD33. In the present study, we asked whether leukaemic stem cells in patients with AML express CD33.Materials and methods: A multicolour-staining technique was applied in 11 patients with AML, and leukaemic progenitors defined as CD34(+)/CD38(-)/CD123(+) cells. AML stem cells were purified by cell sorting and were examined for expression of CD33 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR).Results: In all patients in whom the majority of myeloblasts expressed CD33 (n = 8), AML progenitors reacted with the CD33 antibody P67.6. Repopulation experiments utilizing irradiated NOD/SCID mice confirmed that AML stem cells in these patients reside within the CD33(+) subpopulation of the leukaemic clone. Moreover, highly purified AML stem cells (> 98% purity) from patients with CD33(+) AML were found to express CD33 mRNA in RT-PCR analyses. CD33 was neither detectable on CD34(+)/CD38(-) cells in normal bone marrow nor on leukaemic stem cells in patients with CD33-negative AML.Conclusions: Leukaemic stem cells in patients with CD33(+) AML express CD33. This observation is in favour of novel treatment concepts employing CD33-targeting antibodies in AML.