Dear Editor,
We read with great interest the article by Yang Y, et al., “Sirolimus modulates the erythroid differentiation of K562 cells by upregulating SHP1,” published in your journal on 19 August 2025 [1]. The article discusses the effect of sirolimus on erythroid differentiation in K562 cells mediated by SHP1. Transient transfection was used to verify that SHP1 silencing inhibited K562 cell differentiation and that sirolimus reversed this effect.
The article combines multiple experimental methods, rendering the conclusions rigorous and reliable. This also leads me to think about some issues related to the use of sirolimus. Firstly, the results of the CCK-8 assays showed that sirolimus inhibited the proliferation of K562 cells and promoted their differentiation. The K562 cell line is derived from a patient with chronic myeloid leukemia, suggesting that sirolimus could be used to promote the differentiation of leukemia cells, thereby contributing to research on treating leukemia. Secondly, the experimental results in the article indicated that sirolimus reduced the expression of mTOR and p-mTOR in K562 cells, both of which are associated with autophagy. Given the close relationship between autophagy and differentiation, we hypothesize that sirolimus may influence the differentiation of K562 cells by regulating autophagy [2]. Finally, Saraswati et al. reported that phloretin regulated the SHP1/STAT3 pathway and inhibited the growth of liver cancer cells [3], while inhibiting the expression of STAT3 in HEL erythroleukemia cells can induce apoptosis [4]. Therefore, we speculate that sirolimus may inhibit the growth of K562 cells via the SHP1/STAT3 pathway. However, due to differences in both the drugs and cell lines used, further experiments are needed to verify whether sirolimus acts through the SHP1/STAT3 pathway in leukemia cell lines other than HEL (including K562).
We are extremely grateful for the opportunity to share our views and would be happy to engage in academic exchanges. We are also very grateful to the authors for providing us with research ideas through their experimental results.
Yours sincerely.
Author contributions
Ying Liu searched for literature materials and wrote the main manuscript text, while Yanna Zhao revised the content of the article.
Funding
No specific grant supported this research.
Data availability
No data was used for the research described in the article.
Declarations
Competing interests
The authors declare no competing interests.
Footnotes
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References
- 1.Yang Y, Tang Z, Hu Q, Yang C, Chen M, Jing H, Han B (2025) Sirolimus modulates the erythroid differentiation of K562 cells by upregulating SHP1. Ann Hematol. Aug 19 [DOI] [PMC free article] [PubMed]
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- 4.Song JR, Niu ZP, Yang K, Wang L, Huang YB, Rao Q, Liu HY, Hao XJ, Li YM (2024) A natural acylphloroglucinol exerts anti-erythroleukemia effects via targeting STAT3 and p38-MAPK, and inhibiting PI3K/AKT/mTOR signaling pathway. Biomed Pharmacother 180:117424 [DOI] [PubMed] [Google Scholar]
Associated Data
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Data Availability Statement
No data was used for the research described in the article.