Leukemic Environment Alters Neutrophils Worsening Disease Progression

Abstract Acute Myeloid Leukemia (AML) is the abnormal differentiation of hematopoietic stem cells in bone marrow into malignant blasts. The leukemic environment plays an important role during disease progression, by shaping immune landscape interacting with these Mounting evidence suggests neutrophils are complicit within tumors enhancing tumorigenesis and immunosuppression; however, little known about how contribute to AML even though comprise half cellularity. Tumor-associated found overactivated state, constantly releasing pro-inflammatory cytokines granular proteins promote tumorigenesis. Therefore, we investigated neutrophil phenotype our chimeric mouse model. We observed were also activated state. More importantly, sorted leukemic-exposed more susceptible degranulation upon stimulation. Next, single-cell RNA data showed that had higher expression ELANE, a gene encoding elastase (NE). Increased NE levels have been associated increased tumor burden many cancers. Although increase inflammation which drives tumorigenesis, it may directly blast proliferation. By targeting model using anti-Ly6G antibody, decreased frequency blasts depleted mice. Also, there was reduced Lin-ckit +CD16/32 +leukemic cells. hypothesize over-activated drive progression BM NE, providing new avenue for intervention.