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Arsenic trioxide and all-trans retinoic acid suppress the expression of FLT3-ITD.
Leuk Lymphoma. 2020 Jun 14 [Online ahead of print]LL

Abstract

The prognosis of patients with acute myeloid leukemia (AML) caused by the FLT3-ITD mutation is poor. Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) can down-regulate FLT3-ITD level and selectively kill leukemia cells carrying the FLT3-ITD mutation. However, the mechanisms of action of these two compounds are unknown. Here, we found that ATO could bind FLT3-ITD at Lys91 and Asp225, whereas ATRA could bind FLT3-ITD at Lys5 and Gln6. Both compounds could not bind wild-type FLT3. Further studies revealed that ATO/ATRA may suppress the Expression of FLT3-ITD by promoting the UBE2L6-mediated ubiquitination pathway and decreasing the expression of C-MYC. However, further studies are needed to define the mechanisms of these compounds on AML. Our research provides an experimental basis for the use of ATO/ATRA in FLT3-ITD AML in clinical practice.

Authors+Show Affiliations

Department of Pediatrics, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.Department of Pediatrics, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.Department of Pediatrics, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.Department of Pediatrics, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.Department of Pediatrics, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.Department of Pediatrics, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.Department of Pediatrics, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.Department of Pediatrics, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.Department of Pediatrics, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.Department of Pediatrics, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.Department of Pediatrics, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.Department of Pediatrics, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32536235

Citation

Liang, Cong, et al. "Arsenic Trioxide and All-trans Retinoic Acid Suppress the Expression of FLT3-ITD." Leukemia & Lymphoma, 2020, pp. 1-8.
Liang C, Peng CJ, Wang LN, et al. Arsenic trioxide and all-trans retinoic acid suppress the expression of FLT3-ITD. Leuk Lymphoma. 2020.
Liang, C., Peng, C. J., Wang, L. N., Li, Y., Zheng, L. M., Fan, Z., Huang, D. P., Tang, W. Y., Zhang, X. L., Huang, L. B., Tang, Y. L., & Luo, X. Q. (2020). Arsenic trioxide and all-trans retinoic acid suppress the expression of FLT3-ITD. Leukemia & Lymphoma, 1-8. https://doi.org/10.1080/10428194.2020.1775212
Liang C, et al. Arsenic Trioxide and All-trans Retinoic Acid Suppress the Expression of FLT3-ITD. Leuk Lymphoma. 2020 Jun 14;1-8. PubMed PMID: 32536235.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Arsenic trioxide and all-trans retinoic acid suppress the expression of FLT3-ITD. AU - Liang,Cong, AU - Peng,Chun-Jin, AU - Wang,Li-Na, AU - Li,Yu, AU - Zheng,Li-Min, AU - Fan,Zhong, AU - Huang,Dan-Ping, AU - Tang,Wen-Yan, AU - Zhang,Xiao-Li, AU - Huang,Li-Bin, AU - Tang,Yan-Lai, AU - Luo,Xue-Qun, Y1 - 2020/06/14/ PY - 2020/6/16/entrez KW - Degradation KW - FLT3-ITD KW - acute myeloid leukemia KW - all-trans-retinoic acid KW - arsenic trioxide SP - 1 EP - 8 JF - Leukemia & lymphoma JO - Leuk. Lymphoma N2 - The prognosis of patients with acute myeloid leukemia (AML) caused by the FLT3-ITD mutation is poor. Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) can down-regulate FLT3-ITD level and selectively kill leukemia cells carrying the FLT3-ITD mutation. However, the mechanisms of action of these two compounds are unknown. Here, we found that ATO could bind FLT3-ITD at Lys91 and Asp225, whereas ATRA could bind FLT3-ITD at Lys5 and Gln6. Both compounds could not bind wild-type FLT3. Further studies revealed that ATO/ATRA may suppress the Expression of FLT3-ITD by promoting the UBE2L6-mediated ubiquitination pathway and decreasing the expression of C-MYC. However, further studies are needed to define the mechanisms of these compounds on AML. Our research provides an experimental basis for the use of ATO/ATRA in FLT3-ITD AML in clinical practice. SN - 1029-2403 UR - https://www.unboundmedicine.com/medline/citation/32536235/Arsenic_trioxide_and_all-trans_retinoic_acid_suppress_the_expression_of_FLT3-ITD L2 - http://www.tandfonline.com/doi/full/10.1080/10428194.2020.1775212 DB - PRIME DP - Unbound Medicine ER -
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