原创力文档sall4, a stem cell factor, affects the side population by regulation of the atp-binding cassette drug transport genessall4,干细胞因子,影响人口的调节腺苷盒式药物运输基因.pdfVIP
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sall4, a stem cell factor, affects the side population by regulation of the atp-binding cassette drug transport genessall4,干细胞因子,影响人口的调节腺苷盒式药物运输基因
SALL4, a Stem Cell Factor, Affects the Side Population by
Regulation of the ATP-Binding Cassette Drug Transport
Genes
1. 2. 1 1 1 1 1 2
Ha-Won Jeong , Wei Cui , Youyang Yang , Jiayun Lu , Jie He , Ailing Li , David Song , Ye Guo , Bee H.
3 1
Liu , Li Chai *
1The Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Department of Clinical
Laboratory, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China, 3 Centre for Life Sciences, Cancer Science Institute of Singapore,
National University of Singapore, Singapore, Singapore
Abstract
Our previous work shows that the stem cell factor SALL4 plays a central role in embryonic and leukemic stem cells. In this
study, we report that SALL4 expression was higher in drug resistant primary acute myeloid leukemic patients than those
from drug-responsive cases. In addition, while overexpression of SALL4 led to drug resistance in cell lines, cells with
decreased SALL4 expression were more sensitive to drug treatments than the parental cells. This led to our investigation of
the implication of SALL4 in drug resistance and its role in side population (SP) cancer stem cells. SALL4 expression was
higher in SP cells compared to non-SP cells by 2–4 fold in various malignant hematopoietic cell lines. Knocking down of
SALL4 in isolated SP cells resulted in a reduction of SP cells, indicating that SALL4 is required for their self-renewal. The SP
phenotype is known to be mediated by members of the ATP-binding cassette (ABC) drug transport protein family, such as
ABCG2 and ABCA3. Using chromatin-immunoprecipitation
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