SALL4 is a key regulator of survival and apoptosis in human leukemic cells
Open accessAbstract
Increasing studies suggest that SALL4 may play vital roles in leukemogenesis and stem cell phenotypes. We have mapped the global gene targets of SALL4 using chromatin immunoprecipitation followed by microarray hybridization and identified more than 2000 high-confidence, SALL4-binding genes in the human acute promyelocytic leukemic cell line, NB4. Analysis of SALL4-binding sites reveals that genes involved in cell death, cancer, DNA replication/repair, and cell cycle were highly enriched (P < .05). These genes include 38 important apoptosis-inducing genes (TNF, TP53, PTEN, CARD9, CARD11, CYCS, LTA) and apoptosis-inhibiting genes (Bmi-1, BCL2, XIAP, DAD1, TEGT). Real-time polymerase chain reaction has shown that expression levels of these genes changed significantly after SALL4 knockdown, which ubiquitously led to cell apoptosis. Flow cytometry revealed that reduction of SALL4 expression in NB4 and other leukemia cell lines dramatically increased caspase-3, annexin V, and DNA fragmentation activity. Bromodeoxyuridine-incorporation assays showed decreased numbers of S-phase cells and increased numbers of G1- and G2-phase cells indicating reduced DNA synthesis, consistent with results from cell proliferation assays. In addition, NB4 cells that express low levels of SALL4 have significantly decreased tumorigenecity in immunodeficient mice. Our studies provide a foundation in the development of leukemia stem cell-specific therapy by targeting SALL4.
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Constitutive expression of SALL4 contributes to leukemogenesis in adult mice by activating Bmi-1.
“we have shown that constitutive expression of SALL4 contributes to leukemogenesis in adult mice by activating Bmi-1 [42]”
From Stem Cell Factor SALL4 Represses the Transcriptions of PTEN and SALL1 through an Epigenetic Repressor Complex (2009) · cites this paper as [42]
SALL4 is essential for the survival of leukemic cells, and the apoptotic phenotype caused by down-regulation of SALL4 can be rescued by overexpression of Bmi-1.
“Parallel loss-of-function studies have also demonstrated that SALL4 is essential for the survival of leukemic cells, and the apoptotic phenotype that is caused by down-regulation of SALL4 can be rescued by overexpression of Bmi-1 [44].”
From Stem Cell Factor SALL4 Represses the Transcriptions of PTEN and SALL1 through an Epigenetic Repressor Complex (2009) · cites this paper as [44]
Cites
Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells.
Park, I.-K., Qian, D., Kiel, M., Becker, M. W., Pihalja, M., Weissman, I. L., Morrison, S. J., & Clarke, M. F. (2003) · Nature · doi:10.1038/nature01587 · Cited by 1,871 · see citing works
Al-Baradie, R., Yamada, K., St. Hilaire, C., Chan, W.-M., Andrews, C., McIntosh, N., Nakano, M., Martonyi, E. J., Raymond, W. R., Okumura, S., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/343821 · Cited by 314 · see citing works
Murine inner cell mass-derived lineages depend on Sall4 function
Elling, U., Klasen, C., Eisenberger, T., Anlag, K., & Treier, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607884103 · Cited by 186 · see citing works
Kohlhase, J., Schuh, R., Dowe, G., Kühnlein, R. P., Jäckle, H., Schroeder, B., Schulz-Schaeffer, W., Kretzschmar, H. A., Köhler, A., Müller, U., et al. (1996) · Genomics · doi:10.1006/geno.1996.0631 · Cited by 145 · see citing works
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Lu, J., Jeong, H., Kong, N., Yang, Y., Carroll, J., Luo, H. R., Silberstein, L. E., YupoMa, & Chai, L. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005577 · Cited by 168 · see citing works
“In addition, we have shown that constitutive expression of SALL4 contributes to leukemogenesis in adult mice by activating Bmi-1 [42], a key regulator in hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs) [43].”
Self-citationSALL4, the missing link between stem cells, development and cancer
Tatetsu, H., Kong, N. R., Chong, G., Amabile, G., Tenen, D. G., & Chai, L. (2016) · Gene · doi:10.1016/j.gene.2016.02.019 · Cited by 130 · see citing works
Self-citationRole of SALL4 in the progression and metastasis of colorectal cancer
Forghanifard, M. M., Moghbeli, M., Raeisossadati, R., Tavassoli, A., Mallak, A. J., Boroumand-Noughabi, S., & Abbaszadegan, M. R. (2013) · Journal of Biomedical Science · doi:10.1186/1423-0127-20-6 · Cited by 82 · see citing works
Gao, C., Dimitrov, T., Yong, K. J., Tatetsu, H., Jeong, H.-W., Luo, H. R., Bradner, J. E., Tenen, D. G., & Chai, L. (2013) · Blood · doi:10.1182/blood-2012-04-424275 · Cited by 65 · see citing works
Self-citationSALL4 is a key transcription regulator in normal human hematopoiesis
Gao, C., Kong, N. R., Li, A., Tatetu, H., Ueno, S., Yang, Y., He, J., Yang, J., Ma, Y., Kao, G. S., et al. (2013) · Transfusion · doi:10.1111/j.1537-2995.2012.03888.x · Cited by 58 · see citing works
Self-citationLiu, T.-C., Vachharajani, N., Chapman, W. C., & Brunt, E. M. (2014) · American Journal of Surgical Pathology · doi:10.1097/pas.0000000000000218 · Cited by 37 · see citing works
SALL4: An Intriguing Therapeutic Target in Cancer Treatment
Moein, S., Tenen, D. G., Amabile, G., & Chai, L. (2022) · Cells · doi:10.3390/cells11162601 · Cited by 35 · see citing works
Self-citationRole of SALL4 in hematopoiesis
Yang, J., Liao, W., & Ma, Y. (2012) · Current Opinion in Hematology · doi:10.1097/moh.0b013e328353c684 · Cited by 17 · see citing works
Self-citationLeukemic survival factor SALL4 contributes to defective DNA damage repair
Wang, F., Gao, C., Lu, J., Tatetsu, H., Williams, D. A., Müller, L. U., Cui, W., & Chai, L. (2016) · Oncogene · doi:10.1038/onc.2016.146 · Cited by 17 · see citing works
Self-citation
- Authors
- Yang, J., Chai, L., Gao, C., Fowles, T. C., Alipio, Z., Dang, H., Xu, D., Fink, L. M., Ward, D. C., & Ma, Y.
- Affiliations
- Division of Laboratory Medicine, Nevada Cancer Institute, Las Vegas; and
- Brigham and Women's Hospital (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2008-08-01
- Volume
- 112
- Issue
- 3
- Pages
- 805-813
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC2481537
- OpenAlex
- W2136410889
- Cited by
- 132
- References
- 4
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 5 · 2022: 5 · 2021: 8 · 2020: 8 · 2019: 3 · 2018: 9 · 2017: 4 · 2016: 11 · 2015: 10 · 2014: 8 · 2013: 11 · 2012: 9
- FWCI
- 7.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL087948)
- National Cancer Institute (K08CA097185, R21CA131522)
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK063220)
- National Center for Research Resources (P20RR016464)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Keywords
- SALL4, acute promyelocytic leukemia, NB4 cells, apoptosis, cell survival, chromatin immunoprecipitation, caspase-3, cell cycle, cell proliferation, tumorigenicity, leukemia stem cells, gene expression profiling
- MeSH terms
- Animals, Binding Sites, Cell Survival, Humans, Transcription Factors, Leukemia, Promyelocytic, Acute, Gene Expression Regulation, Neoplastic, Mice, SCID, Apoptosis, Gene Expression Profiling, Xenograft Model Antitumor Assays, Cell Line, Tumor, Mice
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