PROJECT SUMMARY

Myelodysplastic Syndrome (MDS) is a blood disorder in which the bone marrow fails to produce enough healthy blood cells. In some patients, hyperinflammation accelerates MDS progression to acute myeloid leukemia (AML), an aggressive cancer with poor survival rates. This hyperinflammation resembles hemophagocytic lymphohistiocytosis (HLH), where an overactive immune system causes severe organ damage. Our research suggests that hyperinflammation in MDS involves similar mechanisms driven by innate and adaptive immune responses.

To detect hyperinflammation early, we developed the OHI (Optimized HLH Inflammatory) index, introduced in Blood (2022). The OHI index uses two blood markers—soluble CD25 and ferritin—to identify high-risk patients. A positive OHI index in MDS predicts worse outcomes and correlates with genetic abnormalities, such as trisomy 8 and deletion 20q.

We propose using the OHI index as a screening tool to identify MDS patients with hyperinflammation who may benefit from targeted therapies. Our research focuses on:

1. Genetic Correlations and outcomes: Using the OHI index to analyze blood samples from MDS patients and study its relationship with genetic mutations.
2. Immune Profiling: Investigating immune cells and inflammatory proteins in OHI-positive versus OHI-negative patients to identify therapeutic targets.

By uncovering the mechanisms driving hyperinflammation, we aim to develop personalized therapies and prevent AML progression and early mortality.