Gene expression profile of HSC/Ps and mature myeloid cells in HMGA2-OE MDS mutant clone
Although HMGA2 overexpression (OE) has been reported in several myeloid malignancies, its role in MDS remains unclear. To determine the role of HMGA2 in MDS pathogenesis, we generated MDS mice using patient-derived RUNX1 mutant, and overexpressed HMGA2 in this model. HMGA2-OE MDS mice developed non-infectious pneumonia. Prominent infiltration of neutrophils was observed in the lung tissue. RNA sequencing of HSC/Ps and neutrophils revealed that genes related to platelet activation are significantly activated in HMGA2-OE MDS mice. Flow cytometric analysis showed that P-selectin+ activated platelets tightly interact with neutrophils in the HMGA2-OE MDS mice. Genetic inhibition of P-selectin attenuated neutrophil activation and pneumonia development in the MDS mice.  These findings provide new insights into mechanistic basis of systemic complications of MDS. Overall design: Expression profiles of mRNA in HSC/Ps and Ly6G+ myeloid cells from RUNX1 mutant mice with or without HMGA2-OE and their control mice.