Spns3, or spinster homolog 3, belongs to the Spinster (SPNS) family. It is involved in sphingolipid transportation across the cell membrane and may play a role in the Sphingosine-1-phosphate signal pathway, which is important for maintaining the acute myeloid leukemia (AML) microenvironment [1]. Vertebrates have three spinster orthologs including Spns3, and Spin proteins are generally localized in lysosomes and participate in the late stages of the autophagic process [3].

In AML, high Spns3 expression is associated with apoptosis resistance and poor prognosis. Internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3-ITD) mutation and the AC127521.1/MIR-139/Spns3 competing endogenous RNA axis regulate Spns3 expression [1]. Also, in pediatric AML patients with FLT3-ITD mutation, upregulation of Spns3 predicts poor prognosis [2]. In chemotherapy-only AML patients, high Spns3 expression has adverse effects on event-free survival (EFS) and overall survival (OS), and in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) group, high Spns3 expression is significantly associated with OS [4].

In conclusion, Spns3 is significant in sphingolipid transportation and the Sphingosine-1-phosphate signal pathway. Its high expression in AML is related to apoptosis resistance and poor prognosis, making it a potential prognostic biomarker. Research on Spns3 in AML helps understand the disease mechanism and may provide new strategies for treatment [1,2,4].

References:

1. Hong, Yang, Tian, Xiaopeng, Wang, Mengmiao, Chen, Cheng, Sun, Aining. . Bioinformatics-based identification of SPNS3 (Spinster homolog 3) as a prognostic biomarker of apoptosis resistance in acute myeloid leukemia. In Bioengineered, 12, 7837-7848. doi:10.1080/21655979.2021.1982303. https://pubmed.ncbi.nlm.nih.gov/34608834/

2. Eshibona, Nasr, Giwa, Abdulazeez, Rossouw, Sophia Catherine, Christoffels, Alan, Bendou, Hocine. 2022. Upregulation of FHL1, SPNS3, and MPZL2 predicts poor prognosis in pediatric acute myeloid leukemia patients with FLT3-ITD mutation. In Leukemia & lymphoma, 63, 1897-1906. doi:10.1080/10428194.2022.2045594. https://pubmed.ncbi.nlm.nih.gov/35249471/

3. Nakano, Yoshiro. 2019. Stories of spinster with various faces: from courtship rejection to tumor metastasis rejection. In Journal of neurogenetics, 33, 90-95. doi:10.1080/01677063.2019.1586897. https://pubmed.ncbi.nlm.nih.gov/30939968/

4. Huang, Wenhui, Qian, Tingting, Cheng, Zhiheng, Cui, Longzhen, Fu, Lin. 2020. Prognostic significance of Spinster homolog gene family in acute myeloid leukemia. In Journal of Cancer, 11, 4581-4588. doi:10.7150/jca.44766. https://pubmed.ncbi.nlm.nih.gov/32489475/