ArticleExperimental hematology2011
Flt3-ITD alters chemotherapy response in vitro and in vivo in a p53-dependent manner.
Article in Experimental hematology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Prognostication refinement in NPM1-mutated acute myeloid leukemia stratified by FLT3-ITD status with different induction doses of cytarabine.Cancer medicine · 2023Article
- Targeted inhibition of cooperative mutation- and therapy-induced AKT activation in AML effectively enhances response to chemotherapy.Leukemia · 2021Article
- Targeting of PI3K/AKT signaling and DNA damage response in acute myeloid leukemia: a novel therapeutic strategy to boost chemotherapy response and overcome resistance.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- Targeting Glutamine Metabolism and Redox State for Leukemia Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- A Phase I Study of CPI-613 in Combination with High-Dose Cytarabine and Mitoxantrone for Relapsed or Refractory Acute Myeloid Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Article
- A Small-Molecule Inhibitor of WEE1, AZD1775, Synergizes with Olaparib by Impairing Homologous Recombination and Enhancing DNA Damage and Apoptosis in Acute Leukemia.Molecular cancer therapeutics · 2017Article
- The applications of the novel polymeric fluoropyrimidine F10 in cancer treatment: current evidence.Future oncology (London, England) · 2016Review
- Internal tandem duplication and tyrosine kinase domain mutations inBiomedical reports · 2016Article
- Targeted Therapy of FLT3 in Treatment of AML-Current Status and Future Directions.Journal of clinical medicine · 2014Review
- Inhibition of Wee1 sensitizes cancer cells to antimetabolite chemotherapeutics in vitro and in vivo, independent of p53 functionality.Molecular cancer therapeutics · 2013Article
- Animal models of leukemia: any closer to the real thing?Cancer metastasis reviews · 2013Review
- Replication-dependent irreversible topoisomerase 1 poisoning is responsible for FdUMP[10] anti-leukemic activity.Experimental hematology · 2013Article
- EVI1 inhibits apoptosis induced by antileukemic drugs via upregulation of CDKN1A/p21/WAF in human myeloid cells.PloS one · 2013Article
- Article
- Correlation analysis of p53 protein isoforms with NPM1/FLT3 mutations and therapy response in acute myeloid leukemia.Oncogene · 2012Article
- Targeting MCL-1 sensitizes FLT3-ITD-positive leukemias to cytotoxic therapies.Blood cancer journal · 2012Article
- Overexpression of MN1 confers resistance to chemotherapy, accelerates leukemia onset, and suppresses p53 and Bim induction.PloS one · 2012Article
- An integrated approach to dissecting oncogene addiction implicates a Myb-coordinated self-renewal program as essential for leukemia maintenance.Genes & development · 2011Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveThe FLT3 internal tandem duplication (Flt3-ITD) confers a worse prognosis for patients with acute myeloid leukemia (AML); however, the mechanisms involved are unknown. As AML is treated with cytarabine (Ara-C) and an anthracycline, we sought to determine the effects of the Flt3-ITD on response to these agents. MATERIALS AND
methodsA genetically defined mouse model of AML was used to examine the effects of the Flt3-ITD on response to cytarabine and doxorubicin in vitro and in vivo.
resultsIn vitro, the Flt3-ITD conferred resistance to doxorubicin and doxorubicin plus Ara-C, but sensitivity to Ara-C alone. This resistance was reversible by the Flt3-ITD inhibitor sorafenib. The Flt3-ITD did not affect DNA damage levels after treatment, but was associated with increased levels of p53. The p53 response was critical to the observed changes as the Flt3-ITD had no effect on chemotherapy response in the setting of p53 null AML. In vivo, the Flt3-ITD accelerated engraftment that was partially reversible by Ara-C but not doxorubicin. Additionally, Ara-C provided a significant reduction in disease burden and a survival advantage that was not increased by the addition of doxorubicin. Doxorubicin alone led to only minimal disease reduction and no survival benefit.
conclusionsThese data demonstrate that the Flt3-ITD confers sensitivity to Ara-C, but resistance to doxorubicin in a manner that depends on p53. Thus, patients with Flt3-ITD positive AML may not benefit from treatment with an anthracycline.
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