Fleischman Lab

University of California-Irvine

INTERNAL MEDICINE/MEDICINE

Irvine · United States

NIH-funded
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NIH R01 · 2024

Role of IL-10R signaling in inflammation induced exhaustion of HSC and emergence of JAK2V617F clonal hematopoiesis

Revised Project Summary Age and chronic inflammatory stress drive the emergence of mutant bone marrow stem cells that can lead to specific hematologic malignancy associated mutations allow HSC to resist specific stressors could be leveraged toward therapies aimed at neutralizing the selective advantage of the malignant clone. We have recently found that patients with myeloproliferative neoplasm (MPN) have a dampened response to the anti-inflammatory cytokine IL-10 and this leads to persistent production of the inflammatory cytokine TNFα. In a murine Jak2V617F MPN model, pharmacologic blockade of IL-10R signaling enhances the selective advantage of Jak2V617F mutant cells. The objective of…

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