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Targeting of STAT5 using the small molecule topotecan hydrochloride suppresses acute myeloid leukemia progression

  • Authors:
    • Jiahui Li
    • Bin Tang
    • Ying Miao
    • Guihong Li
    • Zhenliang Sun
  • View Affiliations / Copyright

    Affiliations: Fengxian Hospital Affiliated to Anhui University of Science and Technology, Shanghai 201499, P.R. China, Department of Gynecology, East China Normal University Wuhu Affiliated Hospital (The Second People's Hospital of Wuhu City), Wuhu, Anhui 241000, P.R. China, East China Normal University and Shanghai Fengxian District Central Hospital Joint Center for Translational Medicine, Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 201100, P.R. China, Fengxian Hospital Affiliated to The Southern Medical University, Shanghai 201499, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 208
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    Published online on: October 11, 2023
       https://doi.org/10.3892/or.2023.8645
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Abstract

Acute myeloid leukemia (AML) is a common type of acute leukemia in adults and relapse is one of the main reasons for treatment failure. FLT3‑ITD mutations are associated with poor prognosis, short disease‑free progression survival and high relapse rates in patients with AML. STAT5 is activated by FLT3‑ITD and drives the pathogenesis of AML. STAT5 activation is usually a hallmark of hematologic malignancies and occurs in ~70% of patients with AML. Moreover, STAT5 is a key molecule which regulates hematopoiesis, and its high expression is closely associated with drug resistance, thus direct targeting of STAT5 for AML is of great clinical value. The present study introduces a new small‑molecule inhibitor that targets STAT5, presenting a promising approach for AML therapy. A high throughput fluorescence polarization (FP) screening system for STAT5 was designed and established, and used to screen an existing compound library to obtain the highly active small molecule inhibitor, topotecan hydrochloride. Topotecan hydrochloride was demonstrated to be an effective inhibitor of STAT5 by molecular docking prediction and cellular thermal shift assay. Topotecan hydrochloride bound to STAT5, inhibiting its dimerization, phosphorylation and transcription of specific target genes. The compound exhibits cellular activity at the nanomolar level and significantly inhibits the proliferation of human AML cell lines and FLT3‑ITD+ AML cells. Furthermore, topotecan hydrochloride has the potential to exert an anti‑tumor effect in vivo. Overall, topotecan hydrochloride offers a new opportunity for the treatment of AML and other hematologic malignancies by directly targeting STAT5.
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Copy and paste a formatted citation
Spandidos Publications style
Li J, Tang B, Miao Y, Li G and Sun Z: Targeting of STAT5 using the small molecule topotecan hydrochloride suppresses acute myeloid leukemia progression. Oncol Rep 50: 208, 2023.
APA
Li, J., Tang, B., Miao, Y., Li, G., & Sun, Z. (2023). Targeting of STAT5 using the small molecule topotecan hydrochloride suppresses acute myeloid leukemia progression. Oncology Reports, 50, 208. https://doi.org/10.3892/or.2023.8645
MLA
Li, J., Tang, B., Miao, Y., Li, G., Sun, Z."Targeting of STAT5 using the small molecule topotecan hydrochloride suppresses acute myeloid leukemia progression". Oncology Reports 50.6 (2023): 208.
Chicago
Li, J., Tang, B., Miao, Y., Li, G., Sun, Z."Targeting of STAT5 using the small molecule topotecan hydrochloride suppresses acute myeloid leukemia progression". Oncology Reports 50, no. 6 (2023): 208. https://doi.org/10.3892/or.2023.8645
Copy and paste a formatted citation
x
Spandidos Publications style
Li J, Tang B, Miao Y, Li G and Sun Z: Targeting of STAT5 using the small molecule topotecan hydrochloride suppresses acute myeloid leukemia progression. Oncol Rep 50: 208, 2023.
APA
Li, J., Tang, B., Miao, Y., Li, G., & Sun, Z. (2023). Targeting of STAT5 using the small molecule topotecan hydrochloride suppresses acute myeloid leukemia progression. Oncology Reports, 50, 208. https://doi.org/10.3892/or.2023.8645
MLA
Li, J., Tang, B., Miao, Y., Li, G., Sun, Z."Targeting of STAT5 using the small molecule topotecan hydrochloride suppresses acute myeloid leukemia progression". Oncology Reports 50.6 (2023): 208.
Chicago
Li, J., Tang, B., Miao, Y., Li, G., Sun, Z."Targeting of STAT5 using the small molecule topotecan hydrochloride suppresses acute myeloid leukemia progression". Oncology Reports 50, no. 6 (2023): 208. https://doi.org/10.3892/or.2023.8645
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