Acute Myeloid Leukemia: Mutations Blocking Differentiation Lead to Distinct Leukemic Subtypes

A 70-year-old African-American male presented to the emergency room for 1 month of fatigue, progressive dyspnea on exertion, and easy bruising. He endorsed a past medical history significant for insulin-dependent diabetes, chronic kidney disease, and nonischemic cardiomyopathy. He denied a family history of malignancy and noted he was a retired army mechanic with prior exposure to Agent Orange. At triage, his vital signs were within normal limits. His physical exam revealed pale mucous membranes, a normal cardiopulmonary exam, no hepatosplenomegaly, and trace peripheral edema. A complete blood count showed leukocytosis of 26,450 cells/μL comprised of 2.1% neutrophils, 11.8% lymphocytes, and 86.1% blasts. He had a normocytic anemia with hemoglobin 9.3 g/dL and thrombocytopenia of 18,000 platelets/μL. Coagulation studies identified an elevated international normalized ratio (INR) of 1.6 (normal ≤1.1) and prothrombin time of 17.1 s (normal 8.9–11.4 s) and a decreased fibrinogen of 106 mg/dL (normal 217–420 mg/dL). A peripheral blood smear presented numerous circulating immature myeloid cells intermediate in size with scant cytoplasm, azurophilic granules, and folded nuclei (Fig. 15.1).