Immunological effects of a low-dose cytarabine, aclarubicin and granulocyte-colony stimulating factor priming regimen on a mouse leukemia model.

Abstract

The low-dose cytarabine, aclarubicin and granulocyte-colony stimulating factor (G-CSF) (CAG) priming regimen is an effective treatment for patients with relapsed or refractory acute myeloid leukemia (AML) and advanced myelodysplastic syndrome (MDS). G-CSF influences the bone marrow microenvironment (BMM) by mobilizing regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), as well as by reducing the expression of stromal cell-derived factor-1α (SDF-1α). In the present study, a WEHI-3-grafted BALB/c mouse AML model (AML-M4) was employed to determine how the BMM was altered by different treatment regimens. It was evident that CAG regimen decreased and increased the proportion of Tregs and MDSCs in the bone marrow and spleen, respectively. Furthermore, the CAG regimen downregulated SDF-1α levels in the bone marrow and peripheral blood. However, hematoxylin and eosin staining of the main organs revealed that leukemic cells infiltrated the liver following treatment with the CAG regimen. The present study indicates that the CAG regimen has a positive effect on the immunosuppressive microenvironment in AML and relieves AML-associated BMM immune suppression by decreasing Tregs and MDSCs in the bone marrow and downregulating the SDF-1α/CXCR4 axis in the bone marrow and peripheral blood.

• Authors: Jinqiu Chen, Nan Yang, Hailing Liu, Huan Yao, Jin Wang, Yun Yang, Wanggang Zhang
• Journal: Oncology letters (Oncol Lett) Vol. 16 Issue 3 Pg. 3022-3028 (Sep 2018) ISSN: 1792-1074 [Print] Greece
• PMID: 30127892 (Publication Type: Journal Article)