The novel AML stem cell-associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells
The novel AML stem cell-associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells
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DOI：
10.1182/blood-2007-03-083048
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发表时间：
2007-10-01
期刊：
影响因子：
20.3
通讯作者：
Schuurhuis, Gerrit Jan
中科院分区：
文献类型：
--
作者：
van Rhenen, Anna;van Dongen, Guus A. M. S.;Schuurhuis, Gerrit Jan
在CD34(+)急性髓系白血病(AML)中，恶性干细胞驻留在CD38(-)区室中。我们之前已经证明，诊断时CD34(+)CD38(-)细胞的频率与化疗后微小残留病(MRD)频率以及生存率相关。因此，针对CD34(+)CD38(-)细胞的特异性靶向可能提供治疗选择。此前，我们发现C型凝集素样分子1（CLL-1）在大多数AML病例的整个母细胞室中高表达。我们现在表明，CLL-1 表达也存在于 AML 中的 CD34(+)CD38(-) 干细胞区室中（77/89 名患者）。含有CD34(+)CD38(-)CLL-1(+)细胞的CD34(+)CLL(-)1(+)细胞群确实植入非肥胖糖尿病/严重联合免疫缺陷(NOD/SCID)小鼠中，并长出CLL-1(+)母细胞。 CLL-1 表达在诊断和复发之间没有差异 (n = 9)。缓解期，CLL-1(-)正常细胞和CLL-1(+)恶性CD34+CD38-细胞均存在。高 CLL-1(+) 分数与快速复发相关。正常 (n = 11) 和再生骨髓对照 (n = 6) 的 CD34+CD38- 细胞上完全不表达 CLIL-11。抗CLL-1抗体在所有疾病条件下的AML干细胞特异性以及CD34(+)CLL-1(+)细胞的白血病起始特性表明，抗CLL-1抗体能够实现AML特异性干细胞检测，并可能在未来实现抗原靶向。
In CD34(+) acute myeloid leukemia (AML), the malignant stem cells reside in the CD38(-) compartment. We have shown before that the frequency of such CD34(+)CD38(-) cells at diagnosis correlates with minimal residual disease (MRD) frequency after chemotherapy and with survival. Specific targeting of CD34(+)CD38(-) cells might thus offer therapeutic options. Previously, we found that C-type lectin-like molecule-1 (CLL-1) has high expression on the whole blast compartment in the majority of AML cases. We now show that CLL-1 expression is also present on the CD34(+)CD38(-) stemcell compartment in AML (77/89 patients). The CD34(+)CLL(-)1(+) population, containing the CD34(+)CD38(-)CLL-1(+) cells, does engraft in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with outgrowth to CLL-1(+) blasts. CLL-1 expression was not different between diagnosis and relapse (n = 9). In remission, both CLL-1(-) normal and CLL-1(+) malignant CD34+CD38- cells were present. A high CLL-1(+) fraction was associated with quick relapse. CLIL-11 expression is completely absent both on CD34+CD38- cells in normal (n = 11) and in regenerating bone marrow controls (n = 6). This AML stem-cell specificity of the anti-CLL-1 antibody under all conditions of disease and the leukemia-initiating properties of CD34(+)CLL-1(+) cells indicate that anti-CLL-1 antibody enables both AMLspecific stem-cell detection and possibly antigen-targeting in future.