Bone marrow mesenchymal stem/stromal cells from risk-stratified acute myeloid leukemia patients are anti-inflammatory in in vivo preclinical models of hematopoietic reconstitution and severe colitis.

Acute myeloid leukemia represents a heterogeneous group of disorders characterized by the rapid expansion of immature myeloid cells (blasts) in the bone marrow. There is wide disease heterogeneity and patient risk-stratification principally relies on cytogenetic-molecular data. Bone-marrow mesenchymal stem/stromal cells are key components of the hematopoietic niche thought to contribute to leukemia pathogenesis. We recently reported a correlation between behaviors of bone-marrow mesenchymal stem/stromal cells from acute myeloid leukemia patients in vitro and overall survival. To elaborate on this finding, we investigated the capacity of bone-marrow mesenchymal stem/stromal cells from risk-stratified de novo acute myeloid leukemia patients to regulate the homeostasis of healthy CD34+ hematopoietic stem/progenitor cells, and to exert anti-inflammatory effects in vivo in a pre-clinical model of severe acute colitis. We report that regardless of risk-group, bone-marrow mesenchymal stem/stromal cells from acute myeloid leukemia patients support, similar to those derived from healthy bone-marrow the survival, proliferation, differentiation and clonogenecity of CD34+ cells in vitro, and the in vivo immune deficient mice repopulating assays. Additionally, bone-marrow mesenchymal stem/stromal cells from acute myeloid leukemia patients were capable of reversing the inflammatory phenotype in preclinical models of acute severe colitis, showing a greater anti-inflammatory capacity compared to those derived from healthy bone marrow. Collectively, bone-marrow mesenchymal stem/stromal cells from acute myeloid leukemia patients retain the capacity to support healthy hematopoietic stem/progenitor cells and can suppress inflammation in vivo.