The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Sorafenib treatment of FLT3-ITD+ acute myeloid leukemia: favorable initial outcome and mechanisms of subsequent nonresponsiveness associated with the emergence of a D835 mutation
Open accessAbstract
Internal tandem duplication (ITD) of the fms-related tyrosine kinase-3 (FLT3) gene occurs in 30% of acute myeloid leukemias (AMLs) and confers a poor prognosis. Thirteen relapsed or chemo-refractory FLT3-ITD+ AML patients were treated with sorafenib (200-400 mg twice daily). Twelve patients showed clearance or near clearance of bone marrow myeloblasts after 27 (range 21-84) days with evidence of differentiation of leukemia cells. The sorafenib response was lost in most patients after 72 (range 54-287) days but the FLT3 and downstream effectors remained suppressed. Gene expression profiling showed that leukemia cells that have become sorafenib resistant expressed several genes including ALDH1A1, JAK3, and MMP15, whose functions were unknown in AML. Nonobese diabetic/severe combined immunodeficiency mice transplanted with leukemia cells from patients before and during sorafenib resistance recapitulated the clinical results. Both ITD and tyrosine kinase domain mutations at D835 were identified in leukemia initiating cells (LICs) from samples before sorafenib treatment. LICs bearing the D835 mutant have expanded during sorafenib treatment and dominated during the subsequent clinical resistance. These results suggest that sorafenib have selected more aggressive sorafenib-resistant subclones carrying both FLT3-ITD and D835 mutations, and might provide important leads to further improvement of treatment outcome with FLT3 inhibitors.
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Citations
Cites
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Metadata
- Authors
- Man, C. H., Fung, T. K., Ho, C., Han, H. H. C., Chow, H. C. H., Ma, A. C. H., Choi, W. W. L., Lok, S., Cheung, A. M. S., Eaves, C., Kwong, Y. L., & Leung, A. Y. H.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2012-05-31
- Volume
- 119
- Issue
- 22
- Pages
- 5133-5143
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2017107901
- Cited by
- 279
- References
- 52
- FWCI
- 16.52
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Man, C. H., Fung, T. K., Ho, C., Han, H. H. C., Chow, H. C. H., Ma, A. C. H., Choi, W. W. L., Lok, S., Cheung, A. M. S., Eaves, C., Kwong, Y. L., & Leung, A. Y. H. (2012). Sorafenib treatment of FLT3-ITD+ acute myeloid leukemia: favorable initial outcome and mechanisms of subsequent nonresponsiveness associated with the emergence of a D835 mutation. Blood. https://doi.org/10.1182/blood-2011-06-363960
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
