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v-vi LIST OF FIGURESviii CHAPTER 1: INTRODUCTION AND BACKGROUND1 CHAPTER 2: ESTABLISHING A MORE CLINICALLY RELEVANT MOUSE MODEL OF PATIENT AML AND STANDARD OF CARE CHEMOTHERAPY, TO INVESTIGATE THE THERAPEUTIC POTENTIAL OF ALTERATIONS TO MET/SAM METABOLISM 36 CHAPTER 3: DYSREGULATION OF MET/SAM METABOLISM REGULATE DOT1L EXPRESSION AND FUNCTION; A NOVEL VULNERABILITY IN MLL-FP LEUKEMIA62 CHAPTER 4: OVERALL DISCUSSION AND SUMMARY95 STRENTHS AND LIMITATIONS103 FUTURE DIRECTIONS107 REFERENCES111 ABBREVIATIONS121 CURRICULUM VITAE123

Characterization of a more clinically relevant human leukemia xenograft model to examine perturbation of MET/SAM metabolism as a novel therapeutic paradigm for MLL-R leukemia in vivo.