Hauswirth A W, Florian S, Printz D, Sotlar K, Krauth M-T, Fritsch G, Schernthaner G-H, Wacheck V, Selzer E, Sperr W R, Valent P
Department of Medicine I, Medical University of Vienna, Austria.
Eur J Clin Invest. 2007 Jan;37(1):73-82. doi: 10.1111/j.1365-2362.2007.01746.x.
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.
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).
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.
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.
CD33（唾液酸结合免疫球蛋白样凝集素-3）作为急性髓系白血病（AML）抗体介导治疗的靶点，其重要性日益凸显。在正常髓系造血过程中，CD33的表达仅限于分化的晚期阶段，而原始干细胞不表达CD33。在本研究中，我们探究了AML患者的白血病干细胞是否表达CD33。
对11例AML患者应用多色染色技术，将白血病祖细胞定义为CD34(+)/CD38(-)/CD123(+)细胞。通过细胞分选纯化AML干细胞，并采用逆转录聚合酶链反应（RT-PCR）检测其CD33 mRNA的表达。
在大多数成髓细胞表达CD33的所有患者中（n = 8），AML祖细胞与CD33抗体P67.6发生反应。利用经辐照的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CD33(+)亚群中。此外，在RT-PCR分析中发现，来自CD33(+) AML患者的高度纯化的AML干细胞（纯度> 98%）表达CD33 mRNA。在正常骨髓的CD34(+)/CD38(-)细胞上或CD33阴性AML患者的白血病干细胞上均未检测到CD33。
CD33(+) AML患者的白血病干细胞表达CD33。这一观察结果支持在AML中采用靶向CD33抗体的新型治疗理念。
