Detailed Characterization of Mesenchymal Stem/Stromal Cells from a Large Cohort of AML Patients Demonstrates a Definitive Link to Treatment Outcomes

作者：Diaz de la Guardia Rafael; Lopez Millan Belen; Lavoie Jessie R; Bueno Clara; Castano Julio; Gomez Casares Maite; Vives Susana; Palomo Laura; Juan Manel; Delgado Julio; Blanco Maria L; Nomdedeu Josep; Chaparro Alberto; Luis Fuster Jose; Anguita Eduardo; Rosu Myles Michael; Menendez Pablo

来源：Stem Cell Reports, 2017, 8(6): 1573-1586.

DOI：10.1016/j.stemcr.2017.04.019

Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are key components of the hematopoietic niche thought to have a direct role in leukemia pathogenesis. BM-MSCs from patients with acute myeloid leukemia (AML) have been poorly characterized due to disease heterogeneity. We report a functional, genetic, and immunological characterization of BM-MSC cultures from 46 AML patients, stratified by molecular/cytogenetics into low-risk (LR), intermediate-risk (IR), and high-risk (HR) subgroups. Stable MSC cultures were successfully established and characterized from 40 of 46 AML patients irrespective of the risk subgroup. AML-derived BM-MSCs never harbored tumor-specific cytogenetic/molecular alterations present in blasts, but displayed higher clonogenic potential than healthy donor (HD)derived BM-MSCs. Although HD-and AML-derived BM-MSCs equally provided chemoprotection to AML cells in vitro, AML-derived BM-MSCs were more immunosuppressive/anti-inflammatory, enhanced suppression of lymphocyte proliferation, and diminished secretion of pro-inflammatory cytokines. Multivariate analysis revealed that the level of interleukin-10 produced by AML-derived BM-MSCs as an independent prognostic factor negatively affected overall survival. Collectively our data show that AML-derived BM-MSCs are not tumor related, but display functional differences contributing to therapy resistance and disease evolution.

• 出版日期2017-6-6