title: Re-evaluation of various molecular targets located on CD34+CD38-Lin-leukemia stem cells and other cell subsets in pediatric acute myeloid leukemia.
abstract: Leukemia stem cells (LSCs) are hypothesized to be capable of driving the development of leukemia, and are responsible for disease relapse. Antibody therapy targeting cell surface antigens has significantly improved the treatment outcomes of leukemia. Therefore, it is important to identify cell surface markers that are expressed on LSCs, and that are unexpressed or expressed at reduced levels on normal hematopoietic stem cells (HSCs), in order to establish novel therapeutic targets. In the present study, the immunophenotypic characteristics of cluster of differentiation (CD)34+CD38-lineage (Lin)-stem cells were analyzed, and antigen expression levels were compared with the expression of other cell components, using multicolor flow cytometry, in 54 patients with newly diagnosed acute myeloid leukemia (AML) and 11 control patients with immune thrombocytopenia. The findings indicated that CD133 and human leukocyte antigen (HLA)-DR were expressed on normal HSCs and on AML LSCs, with no significant difference (P>0.05). By contrast, CD33, CD123 and CD44 were highly expressed on AML LSCs, and demonstrated significant differences compared with their expression on normal HSCs (CD33, 81.7 vs. 18.3%; CD123, 75.8 vs. 19.1%; CD44, 97.7 vs. 84.4%). Among the aforementioned antigens, CD33 and CD123 were promising candidates for targeted therapy for the treatment of AML. This was particularly evident for CD123 in immature AML subtype cells, which may require additional investigation within a clinical trial setting. CD44, CD133 and HLA-DR may not be suitable for leukemia targeting due to their broad and high expression levels on normal HSCs and other tissues.
authors: Department of Hematology-Oncology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China.
authors: Yuping
authors: Y
authors: Cheng
authors: Department of Hematology-Oncology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China.
authors: Ming
authors: M
authors: Jia
authors: Department of Hematology-Oncology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China.
authors: Yuanyuan
authors: Y
authors: Chen
authors: Department of Hematology-Oncology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China.
authors: Haizhao
authors: H
authors: Zhao
authors: Department of Hematology-Oncology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China.
authors: Zebin
authors: Z
authors: Luo
authors: Department of Hematology-Oncology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China.
authors: Yongmin
authors: Y
authors: Tang
keywords: childhood acute myeloid leukemia; cluster of differentiation antigen; flow cytometry; hematopoietic stem cells; leukemia stem cells