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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:
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:
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:
1mo
1mo
1mo
Abdel-Wahab Lab, MSKCC
Abdel-Wahab Lab, MSKCC
Abdel-Wahab Lab, MSKCC
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.
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):