Unveiling ILC-poiesis disruption in myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are clonal disorders of hematopoietic stem cells, marked by bone marrow dysplasia, peripheral cytopenia, and variable risk to evolve in acute myeloid leukemia (AML). MDS are highly heterogeneous, with prognoses ranging from a near normal life to severe forms. Despite research advances, MDS pathogenesis is poorly understood, making diagnosis and risk stratification challenging. Growing evidence highlight the role of immune-dysregulation in MDS pathophysiology, although data on its diagnostic or prognostic value are limited. Innate lymphoid cells (ILCs), a family of innate lymphocytes mirroring T cell functions are categorized in helper ILCs (h-ILCs) and cytotoxic ILCs, by means of Natural Killer (NK) cells. ILCs are emerging as regulators of immune tolerance and tumor progression in cancer. We demonstrated the accumulation of ILC precursors and ILC1 in high-risk (HR) patients, along with reduced and functionally impaired NK cells, suggesting disrupted ILC-poiesis. To further investigate this aspect, we performed single cells RNA sequencing on ILCs, precursors and blasts of 3 healthy subjects and 9 MDS patients stratified based on the risk of AML evolution. The first bioinformatic analyses demonstrated that we were able to identify the different group of cells that are differently distributed among the patient groups. Further studies will be focused in investigating the genes differentially expressed in the patient groups.