Internal tandem duplication and tyrosine kinase domain mutations in FLT3 alter the response to daunorubicin in Ba/F3 cells

Takahashi,Shinichiro; Shirahama,Kumi

doi:10.3892/br.2015.541

Internal tandem duplication and tyrosine kinase domain mutations in FLT3 alter the response to daunorubicin in Ba/F3 cells

Authors:
- Shinichiro Takahashi
- Kumi Shirahama
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Affiliations: Division of Hematology, Kitasato University School of Allied Health Sciences, Kanagawa 252‑0373, Japan
Published online on: November 9, 2015 https://doi.org/10.3892/br.2015.541
Pages: 83-86

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Abstract

Internal tandem duplication (ITD) and activating point mutations, mainly at aspartic acid 835 in the tyrosine kinase domain (TKD), are frequently identified in the Fms‑related tyrosine kinase 3 (FLT3) receptor gene in acute myeloid leukemia. The ITD in FLT3 (FLT3‑ITD) confers resistance to several chemotherapeutic drugs; however, the relative effects of FLT3‑ITD and FLT3‑TKD mutations on the efficacy of these drugs have not been reported. In the present study, ITD or TKD mutant forms of FLT3 in Ba/F3 cells were expressed, as in the absence of interleukin‑3 (IL‑3) the growth of these cells is completely dependent on FLT3 oncogenic signals. As a result, the 50% effective dose for daunorubicin was significantly higher in both Ba/F3‑FLT3‑ITD clones, and also in one of the two Ba/F3‑FLT3‑TKD clones when cells were cultured without IL‑3. This phenomenon was not observed for cytarabine in either Ba/F3‑FLT3‑ITD or Ba/F3‑FLT3‑TKD cells. Collectively, these results indicate that ITD and TKD mutations in FLT3 may confer daunorubicin resistance in Ba/F3 cells.

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