This study opens many new research directions for our group and will hopefully be a useful resource for the field. Thanks to Neil Hirsch Foundation, @break_cancer, @ASH_hematology, @BloodCancerUtd, @nih_nhlbi, @theNCI, @TheVFoundation, & Edward P. Evans MDS Foundation.
Excited to present the first pre-print from our group, an investigation the human bone marrow microenvironments in patients with myelodysplastic syndromes (MDS) and normal age-matched subjects using Xenium genotype-informed spatial transcriptomics:
www.biorxiv.org/content/10.6...
Now across a cohort of 41 patients with MDS and 15 bone marrow biopsies from age-matched normal individuals we capture 5.7M cells and identified new cellular niches characteristic of human MDS & lymphoid aggregates unique to MDS marrow:
We identify a mechanism for clonal expansion of MDS through local immunosuppressive effects of MDS mutant cells through secretion of TGFb, as well as cell intrinsic effects as mutant cells themselves have dampened recognition of TGFb (gorgeous art by @DrawImpacts):
Through the use of custom probes we track clonal populations of T cells over time and space in the marrow and identify SF3B1 mutant cells in situ. These studies enabled differential gene expression and niche analyses of clonal cells in tissue:
Led by Susan DeWolf, Rob Stanley, Beatrice Zhang, Kimon Argyropoulos, Stephen Martis & collab with Ben Greenbaum. Prior studies have identified important roles for the microenvironment in MDS but transcriptomic studies of the native marrow in patients with MDS have been limited to date:
