CD33
髓系白血病
川地34
白血病
CD38
造血
骨髓
慢性淋巴细胞白血病
髓样
生物
免疫学
分子生物学
癌症研究
干细胞
遗传学
作者
Alexander B. H. Bakker,Sonja van den Oudenrijn,Arjen Q. Bakker,N Feller,Marja van Meijer,Judith A. Bia,Mandy Jongeneelen,Therèse Visser,Nora Bijl,Cecilia A.W. Geuijen,Wilfred Ε. Marissen,Katarina Radošević,Mark Throsby,Gerrit Jan Schuurhuis,Gert J. Ossenkoppele,John de Kruif,Jaap Goudsmit,Ada M. Kruisbeek
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2004-11-15
卷期号:64 (22): 8443-8450
被引量:203
标识
DOI:10.1158/0008-5472.can-04-1659
摘要
Acute myeloid leukemia (AML) has a poor prognosis due to treatment-resistant relapses. A humanized anti-CD33 antibody (Mylotarg) showed a limited response rate in relapsed AML. To discover novel AML antibody targets, we selected a panel of single chain Fv fragments using phage display technology combined with flow cytometry on AML tumor samples. One selected single chain Fv fragment broadly reacted with AML samples and with myeloid cell lineages within peripheral blood. Expression cloning identified the antigen recognized as C-type lectin-like molecule-1 (CLL-1), a previously undescribed transmembrane glycoprotein. CLL-1 expression was analyzed with a human anti-CLL-1 antibody that was generated from the single chain Fv fragment. CLL-1 is restricted to the hematopoietic lineage, in particular to myeloid cells present in peripheral blood and bone marrow. CLL-1 is absent on uncommitted CD34(+)/CD38(-) or CD34(+)/CD33(-) stem cells and present on subsets of CD34(+)/CD38(+) or CD34(+)/CD33(+) progenitor cells. CLL-1 is not expressed in any other tissue. In contrast, analysis of primary AMLs demonstrated CLL-1 expression in 92% (68 of 74) of the samples. As an AML marker, CLL-1 was able to complement CD33, because 67% (8 of 12) of the CD33(-) AMLs expressed CLL-1. CLL-1 showed variable expression (10-60%) in CD34(+) cells in chronic myelogenous leukemia and myelodysplastic syndrome but was absent in 12 of 13 cases of acute lymphoblastic leukemia. The AML reactivity combined with the restricted expression on normal cells identifies CLL-1 as a novel potential target for AML treatment.
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