3109 - BM-Mscs From Risk-Stratified AML Patients Support Normal Hematopoiesis and are Anti-Inflammatory in in Vivo Preclinical Models of Hematopoietic Reconstitution and Severe Colitis

Abstract

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