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Sox13 and M2-like leukemia-associated macrophages contribute to endogenous IL-34 caused accelerated progression of acute myeloid leukemia

Interleukin 34 (IL-34) mainly plays physiologic and pathologic roles through the sophisticated multi-ligand signaling system, macrophage colony-stimulating factor (M-CSF, CSF-1)/IL-34-CSF-1R axis, which exhibits functional redundancy, tissue-restriction and diversity. This axis is vital for the surv...

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Detalles Bibliográficos
Autores principales: Zhang, Dongyue, Cui, Xiaoxi, Li, Yifei, Wang, Rong, Wang, Hao, Dai, Yibo, Ren, Qian, Wang, Lina, Zheng, Guoguang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10164149/
https://www.ncbi.nlm.nih.gov/pubmed/37149693
http://dx.doi.org/10.1038/s41419-023-05822-z
Descripción
Sumario:Interleukin 34 (IL-34) mainly plays physiologic and pathologic roles through the sophisticated multi-ligand signaling system, macrophage colony-stimulating factor (M-CSF, CSF-1)/IL-34-CSF-1R axis, which exhibits functional redundancy, tissue-restriction and diversity. This axis is vital for the survival, differentiation and function of monocytic lineage cells and plays pathologic roles in a broad range of diseases. However, the role of IL-34 in leukemia has not been established. Here MLL-AF9 induced mouse acute myeloid leukemia (AML) model overexpressing IL-34 (MA9-IL-34) was used to explore its role in AML. MA9-IL-34 mice exhibited accelerated disease progression and short survival time with significant subcutaneous infiltration of AML cells. MA9-IL-34 cells showed increased proliferation. In vitro colony forming assays and limiting dilution transplantation experiments demonstrated that MA9-IL-34 cells had elevated leukemia stem cell (LSC) levels. Gene expression microarray analysis revealed a panel of differential expressed genes including Sex-determining region Y (SRY)-box 13 (Sox13). Furthermore, a positive correlation between the expressions of IL-34 and Sox13 was detected human datasets. Knockdown of Sox13 rescued the enhanced proliferation, high LSC level and subcutaneous infiltration in MA9-IL-34 cells. Moreover, more leukemia-associated macrophages (LAMs) were detected in MA9-IL-34 microenvironment. Additionally, those LAMs showed M2-like phenotype since they expressed high level of M2-associated genes and had attenuated phagocytic potential, suggesting that LAMs should also contribute to IL-34 caused adverse phenotypes. Therefore, our findings uncover the intrinsic and microenvironmental mechanisms of IL-34 in AML and broadens the knowledge of M-CSF/IL-34-CSF-1R axis in malignancies.