The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
FLT3-ITD up-regulates MCL-1 to promote survival of stem cells in acute myeloid leukemia via FLT3-ITD–specific STAT5 activation
Open accessAbstract
Myeloid cell leukemia-1 (MCL-1) is an essential survival factor for hematopoiesis. In humans, hematopoietic stem cells (HSCs) express MCL-1 at the highest level in response to FMS-like tyrosine kinase-3 (FLT3) signaling. We here show that this FLT3-dependent stem cell maintenance system also plays a critical role in survival of leukemic stem cells (LSCs) in acute myeloid leukemia (AML). The CD34+CD38− LSC fraction expresses high levels of FLT3 as well as MCL-1, even compared with normal HSCs. Treatment with FLT3 ligand induced further MCL-1 up-regulation in LSCs in all AML cases tested. Interestingly, the group of samples expressing the highest levels of MCL-1 constituted AML with FLT3–internal tandem duplications (ITD). In FLT3-ITD AML cell lines, cells expressed a high level of MCL-1, and an inhibition of MCL-1 induced their apoptotic cell death. A tyrosine kinase inhibitor suppressed MCL-1 expression, and induced apoptosis that was reversed by the enforced MCL-1 expression. Finally, transduction of FLT3-ITD into HSCs strongly activated MCL-1 expression through its signal transducer and activator of transcription 5 (STAT5)–docking domains. This effect was completely abrogated when STAT5 activation was blocked. Thus, the acquisition of FLT3-ITD ensures LSC survival by up-regulating MCL-1 via constitutive STAT5 activation that is independent of wild-type FLT3 signaling.
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Danial, N. N., & Korsmeyer, S. J. (2004) · Cell · doi:10.1016/s0092-8674(04)00046-7 · Cited by 4,651
Maurer, U., Charvet, C., Wagman, A. S., Dejardin, E., & Green, D. R. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.02.009 · Cited by 881
The role of FLT3 in haematopoietic malignancies
Stirewalt, D. L., & Radich, J. P. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1169 · Cited by 865
Iwasaki, H., Somoza, C., Shigematsu, H., Duprez, E. A., Iwasaki-Arai, J., Mizuno, S.-I., Arinobu, Y., Geary, K., Zhang, P., Dayaram, T., et al. (2005) · Blood · doi:10.1182/blood-2005-03-0860 · Cited by 433
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Cited by
The BCL2 Family: Key Mediators of the Apoptotic Response to Targeted Anticancer Therapeutics
Hata, A. N., Engelman, J. A., & Faber, A. C. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0011 · Cited by 619
Chu, S. H., Heiser, D., Li, L., Kaplan, I., Collector, M., Huso, D., Sharkis, S. J., Civin, C., & Small, D. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.05.027 · Cited by 79
Seipel, K., Marques, M. A. T., Sidler, C., Mueller, B. U., & Pabst, T. (2018) · Haematologica · doi:10.3324/haematol.2018.191650 · Cited by 45
Acquisition of G0 state by CD34-positive cord blood cells after bone marrow transplantation
Shima, H., Takubo, K., Tago, N., Iwasaki, H., Arai, F., Takahashi, T., & Suda, T. (2010) · Experimental Hematology · doi:10.1016/j.exphem.2010.08.004 · Cited by 35
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Metadata
- Authors
- Yoshimoto, G., Miyamoto, T., Jabbarzadeh-Tabrizi, S., Iino, T., Rocnik, J. L., Kikushige, Y., Mori, Y., Shima, T., Iwasaki, H., Takenaka, K., Nagafuji, K., Mizuno, S.-I., Niiro, H., Gilliland, G. D., & Akashi, K.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2009-12-03
- Volume
- 114
- Issue
- 24
- Pages
- 5034-5043
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2030292335
- Cited by
- 272
- References
- 4
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- green
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