Ms4a3, also known as membrane-spanning 4-domains, subfamily A, member 3, is a gene that plays crucial roles in hematopoiesis. It is expressed by granulocyte-monocyte progenitors (GMPs) and is involved in regulating myeloid differentiation, with potential implications in related diseases. Its study has been facilitated by genetic models such as Ms4a3TdT reporter, Ms4a3Cre, and Ms4a3CreERT2 fate-mapping models [1].

Knockdown or deletion of Ms4a3/Ms4a3 promotes TKI resistance and survival of CML cells ex vivo and enhances leukemogenesis in vivo, suggesting that Ms4a3 promotes differentiation in chronic myeloid leukemia by enhancing common β-chain cytokine receptor endocytosis [2]. In addition, in vivo experiments with Ms4a3 knockout mice revealed a slight myeloid differentiation suppression tendency, indicating that Ms4a3 overexpression promotes myeloid differentiation skewing through the activation of the ROS/p38MAPK/TGFβ pathway [3].

In conclusion, Ms4a3 is essential for regulating hematopoietic myeloid differentiation. Model-based research, especially using Ms4a3 knockout mouse models, has revealed its role in chronic myeloid leukemia and provided insights into the underlying mechanisms. These findings may offer potential strategies for treating hematopoietic disorders related to myeloid differentiation [2,3].

References:

1. Liu, Zhaoyuan, Gu, Yaqi, Chakarov, Svetoslav, Su, Bing, Ginhoux, Florent. . Fate Mapping via Ms4a3-Expression History Traces Monocyte-Derived Cells. In Cell, 178, 1509-1525.e19. doi:10.1016/j.cell.2019.08.009. https://pubmed.ncbi.nlm.nih.gov/31491389/

2. Zhao, Helong, Pomicter, Anthony D, Eiring, Anna M, Radich, Jerald P, Deininger, Michael W. . MS4A3 promotes differentiation in chronic myeloid leukemia by enhancing common β-chain cytokine receptor endocytosis. In Blood, 139, 761-778. doi:10.1182/blood.2021011802. https://pubmed.ncbi.nlm.nih.gov/34780648/

3. Dong, Yinping, Yue, Tongpeng, Wang, Xinyue, Zhao, Yu, Li, Deguan. 2024. MS4A3 regulates hematopoietic myeloid differentiation through ROS/TGF-β/p38MAPK pathway. In International immunopharmacology, 143, 113578. doi:10.1016/j.intimp.2024.113578. https://pubmed.ncbi.nlm.nih.gov/39532018/