Myeloproliferative neoplasms (MPNs) are hematologic malignancies that result from a somatic mutation, most commonly in the Janus kinase (JAK2V617F) causing the constitutive activation of the blood cell production pathway, JAK-STAT which leads to an overproduction of mature myeloid cells. Inflammation is a key feature in the development of these blood cancers and drives clinical manifestations. This thesis centers on diet as a non-pharmacologic approach to reduce inflammation. We designed a 15-week clinical trial to test the anti-inflammatory properties of the Mediterranean diet. The trial consists of a two-week “lead-in” period, a ten-week active intervention and a three-week follow up period. Our primary aim is to evaluate the feasibility of a dietary intervention and the adherence to a Mediterranean diet among a MPN cohort. The study’s exploratory endpoints include reduction in inflammatory biomarkers, reduction in symptom burden, and change in the gut microbiome. Our findings demonstrated that a Mediterranean diet is as feasible to follow for MPN patients as the standard US Dietary Guidelines for Americans. We concluded that with dietician counseling and written education MPN patients can achieve proper adherence to a Mediterranean diet. However, there were no specific symptoms being impacted by the Mediterranean diet more than the other. Also, no significant changes on cytokine levels were detected in either of the diet groups throughout the course of the study. Interestingly, we observed that MPN subtype is associated with gut microbiome composition, and that patients with myelofibrosis (MF) had a more dissimilar community composition of microbes in the gut that those suffering from polycythemia vera (PV) or essential thrombocythemia (ET). We also developed mouse models to test the impact of diet on the trajectory of mutant hematopoietic cells. We adapted a mouse bone marrow transplant technique to yield mice with a small percentage of mutant cells in the blood, recapitulating what is seen in humans with clonal hematopoiesis of indeterminate potential (CHIP), a precursor to hematologic malignancy. With our mouse model we did not find that high fat diet (HFD) nor N-acetylcysteine (N-AC) had a significant impact on the trajectory of Tet2-/- cells (a common CHIP mutation)but we did see less weight gain in mice on a HFD + N-AC water.