The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Antileukemic activity of rapamycin in acute myeloid leukemia
Abstract
The mammalian target of rapamycin (mTOR) is a key regulator of growth and survival in many cell types. Its constitutive activation has been involved in the pathogenesis of various cancers. In this study, we show that mTOR inhibition by rapamycin strongly inhibits the growth of the most immature acute myeloid leukemia (AML) cell lines through blockade in G0/G1 phase of the cell cycle. Accordingly, 2 downstream effectors of mTOR, 4E-BP1 and p70S6K, are phosphorylated in a rapamycin-sensitive manner in a series of 23 AML cases. Interestingly, the mTOR inhibitor markedly impairs the clonogenic properties of fresh AML cells while sparing normal hematopoietic progenitors. Moreover, rapamycin induces significant clinical responses in 4 of 9 patients with either refractory/relapsed de novo AML or secondary AML. Overall, our data strongly suggest that mTOR is aberrantly regulated in most AML cells and that rapamycin and analogs, by targeting the clonogenic compartment of the leukemic clone, may be used as new compounds in AML therapy.
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Cites
1 retracted
RETRACTED: Downstream effectors of oncogenic ras in multiple myeloma cells
Hu, L., Shi, Y., Hsu, J.-H., Gera, J., Ness, B. V., & Lichtenstein, A. K. (2003) · Blood · doi:10.1182/blood-2002-08-2640 · Cited by 141
RetractedCellular survival: a play in three Akts
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TOR, a Central Controller of Cell Growth
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Regulation of translation initiation by FRAP/mTOR
Gingras, A.-C., Raught, B., & Sonenberg, N. (2001) · Genes & Development · doi:10.1101/gad.887201 · Cited by 1,545
Chemistry and Biology of the Immunophilins and Their Immunosuppressive Ligands
Schreiber, S. L. (1991) · Science · doi:10.1126/science.1702904 · Cited by 1,494
Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies
Yamamoto, Y. (2001) · Blood · doi:10.1182/blood.v97.8.2434 · Cited by 1,150
Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR
Neshat, M. S., Mellinghoff, I. K., Tran, C., Stiles, B., Thomas, G., Petersen, R., Frost, P., Gibbons, J. J., Wu, H., & Sawyers, C. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.171076798 · Cited by 969
Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy
Wendel, H.-G., Stanchina, E. D., Fridman, J. S., Malina, A., Ray, S., Kogan, S., Cordon-Cardo, C., Pelletier, J., & Lowe, S. W. (2004) · Nature · doi:10.1038/nature02369 · Cited by 951
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Cited by
Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells
Yilmaz, Ö. H., Valdez, R., Theisen, B. K., Guo, W., Ferguson, D. O., Wu, H., & Morrison, S. J. (2006) · Nature · doi:10.1038/nature04703 · Cited by 1,113
The NF1 tumor suppressor critically regulates TSC2 and mTOR
Johannessen, C. M., Reczek, E. E., James, M. F., Brems, H., Legius, E., & Cichowski, K. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503224102 · Cited by 601
Khwaja, A., Bjorkholm, M., Gale, R. E., Levine, R. L., Jordan, C. T., Ehninger, G., Bloomfield, C. D., Estey, E., Burnett, A., Cornelissen, J. J., et al. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.10 · Cited by 592
Martelli, A. M., Nyåkern, M., Tabellini, G., Bortul, R., Tazzari, P. L., Evangelisti, C., & Cocco, L. (2006) · Leukemia · doi:10.1038/sj.leu.2404245 · Cited by 342
Cancer drug discovery by repurposing: teaching new tricks to old dogs
Gupta, S. C., Sung, B., Prasad, S., Webb, L. J., & Aggarwal, B. B. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.06.005 · Cited by 340
Metadata
- Authors
- Récher, C., Beyne-Rauzy, O., Demur, C., Chicanne, G., Dos Santos, C., Mas, V. M.-D., Benzaquen, D., Laurent, G., Huguet, F., & Payrastre, B.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2005-03-15
- Volume
- 105
- Issue
- 6
- Pages
- 2527-2534
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2007757672
- Cited by
- 296
- References
- 53
- FWCI
- 9.44
- Type
- journal article
- Language
- en
- Open access
- closed
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- Récher, C., Beyne-Rauzy, O., Demur, C., Chicanne, G., Dos Santos, C., Mas, V. M.-D., Benzaquen, D., Laurent, G., Huguet, F., & Payrastre, B. (2005). Antileukemic activity of rapamycin in acute myeloid leukemia. Blood. https://doi.org/10.1182/blood-2004-06-2494
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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